diff --git a/README.md b/README.md
index 88080a8..8fd20a9 100644
--- a/README.md
+++ b/README.md
@@ -384,13 +384,22 @@ wiggletools max test/fixedStep.bw test/variableStep.bw
 
 * Welch's t-test
 
-Computes the two-tailed p-value of Welch's t-test comparing to sets of numbers, each assumed to have a normal distribution:
+Computes the two-tailed p-value of Welch's t-test comparing two sets of numbers, each assumed to have a normal distribution:
 
 ```
 wiggletools ttest test/fixedStep.bw test/variableStep.bw test/fixedStep.wig \
             : test/fixedStep.wig test/variableStep.bw test/fixedStep.wig
 ```
 
+* F-test
+
+Computes the p-value of the F-test comparing sets of numbers, each assumed to have a normal distribution:
+
+```
+wiggletools ftest test/fixedStep.bw test/variableStep.bw test/fixedStep.wig \
+            : test/fixedStep.wig test/variableStep.bw test/fixedStep.wig
+```
+
 * Wilcoxon's sum rank test
 
 Non-parametric equivalent of the above:
diff --git a/src/commandParser.c b/src/commandParser.c
index 76d06bd..88b18ac 100644
--- a/src/commandParser.c
+++ b/src/commandParser.c
@@ -42,16 +42,17 @@ puts("\twiggletools program");
 puts("");
 puts("Program grammar:");
 puts("\tprogram = (iterator) | do (iterator) | (extraction)");
-puts("\titerator = (filename) | (unary_operator) (iterator) | (binary_operator) (iterator) (iterator) | (reducer) (multiplex) | (setComparison) (multiplex) (multiplex) | print (statistic)");
+puts("\titerator = (in_filename) | (unary_operator) (iterator) | (binary_operator) (iterator) (iterator) | (reducer) (multiplex) | (setComparison) (multiplex_list) | print (statistic)");
 puts("\tunary_operator = unit | write (output) | write_bg (ouput) | smooth (int) | exp | ln | log (float) | pow (float) | offset (float) | scale (float) | gt (float) | default (float) | isZero | (statistic)");
-puts("\toutput = (filename) | -");
-puts("\tfilename = *.wig | *.bw | *.bed | *.bb | *.bg | *.bam | *.vcf | *.bcf");
+puts("\toutput = (out_filename) | -");
+puts("\tin_filename = *.wig | *.bw | *.bed | *.bb | *.bg | *.bam | *.vcf | *.bcf");
 puts("\tstatistic = AUC | meanI | varI | minI | maxI | stddevI | CVI | pearson (iterator)");
 puts("\tbinary_operator = diff | ratio | overlaps | apply (statistic) | fillIn");
 puts("\treducer = cat | sum | product | mean | var | stddev | entropy | CV | median | min | max");
+puts("\tsetComparison = ttest | ftest | wilcoxon");
+puts("\tmultiplex_list = (multiplex) | (multiplex) : (multiplex_list)");
 puts("\tmultiplex = (iterator_list) | map (unary_operator) (multiplex) | strict (multiplex)");
-puts("\titerator_list = (iterator) : | (iterator) (iterator_list)");
-puts("\tsetComparison = ttest | wilcoxon");
+puts("\titerator_list = (iterator) | (iterator) : (iterator_list)");
 puts("\textraction = profile (output) (int) (iterator) (iterator) | profiles (output) (int) (iterator) (iterator) | histogram (output) (width) (iterator_list) | mwrite (output) (multiplex) | mwrite_bg (output) (multiplex)");
 puts("\t\t| apply_paste (out_filename) (statistic) (bed_file) (iterator)");
 
@@ -302,6 +303,28 @@ static Multiplexer * readMultiplexer() {
 	return readMultiplexerToken(token);
 }
 
+static Multiplexer ** readMultiplexerList(int * count) {
+	size_t buffer_size = 8;
+	char * token;
+	Multiplexer ** multis = (Multiplexer **) calloc(buffer_size, sizeof(Multiplexer*));
+	*count = 0;
+
+	for (token = nextToken(0,0); token != NULL && strcmp(token, ":"); token = nextToken(0,0)) {
+		if (*count == buffer_size) {
+			buffer_size *= 2;
+			multis = (Multiplexer **) realloc(multis, buffer_size * sizeof(Multiplexer*));
+		}
+		multis[(*count)++] = readMultiplexerToken(token);
+	}
+	return multis;
+}
+
+static Multiset * readMultiset() {
+	int count = 0; 
+	Multiplexer ** multis = readMultiplexerList(&count);
+	return newMultiset(multis, count);
+}
+
 static WiggleIterator * readTee() {
 	FILE * file = readOutputFilename();
 	return TeeWiggleIterator(readIterator(), file, false, holdFire);
@@ -496,6 +519,10 @@ static WiggleIterator * readTTest() {
 	return TTestReduction(newMultiset(multis, 2));
 }
 
+static WiggleIterator * readFTest() {
+	return FTestReduction(readMultiset());
+}
+
 static WiggleIterator * readMWUTest() {
 	Multiplexer ** multis = calloc(2, sizeof(Multiplexer *));
 	multis[0] = readMultiplexer();
@@ -600,6 +627,8 @@ static WiggleIterator * readIteratorToken(char * token) {
 		return readOverlap();
 	if (strcmp(token, "ttest") == 0)
 		return readTTest();
+	if (strcmp(token, "ftest") == 0)
+		return readFTest();
 	if (strcmp(token, "wilcoxon") == 0)
 		return readMWUTest();
 	if (strcmp(token, "AUC") == 0)
@@ -623,7 +652,7 @@ static WiggleIterator * readIteratorToken(char * token) {
 	if (strcmp(token, "apply") == 0) 
 		return SelectReduction(readApply(), 0);
 
-	return SmartReader(token);
+	return SmartReader(token, holdFire);
 
 }
 
@@ -701,7 +730,7 @@ static Multiplexer * readApplyPaste() {
 	       exit(1);
 	}
 
-	return PasteMultiplexer(ApplyMultiplexer(SmartReader(infilename), statistics, count, readLastIterator(), strict), infile, outfile, false);
+	return PasteMultiplexer(ApplyMultiplexer(SmartReader(infilename, holdFire), statistics, count, readLastIterator(), strict), infile, outfile, false);
 }
 
 void readPrint() {
diff --git a/src/setComparisons.c b/src/setComparisons.c
index 78d40a3..fb5ea77 100644
--- a/src/setComparisons.c
+++ b/src/setComparisons.c
@@ -130,6 +130,105 @@ WiggleIterator * TTestReduction(Multiset * multi) {
 	return newWiggleIterator(data, &TTestReductionPop, &SetComparisonSeek, NAN);
 }
 
+
+////////////////////////////////////////////////////////
+// F-test
+////////////////////////////////////////////////////////
+
+typedef struct ftestData_st {
+	Multiset * multi;
+	int * counts;
+	double * means;
+	int total_count;
+} FTestData;
+
+void FTestSeek(WiggleIterator * iter, const char * chrom, int start, int finish) {
+	FTestData * data = (FTestData* ) iter->data;
+	seekMultiset(data->multi, chrom, start, finish);
+	pop(iter);
+}
+
+
+void FTestReductionPop(WiggleIterator * wi) {
+	if (wi->done)
+		return;
+
+	FTestData * data = (FTestData *) wi->data;
+	Multiset * multi = data->multi;
+
+	if (multi->done) {
+		wi->done = true;
+		return;
+	}
+
+	// Go to first position where both of the sets have at least one value
+	while (!multi->inplay[0] || !multi->inplay[1]) {
+		popMultiset(multi);
+		if (multi->done) {
+			wi->done = true;
+			return;
+		}
+	}
+	wi->chrom = multi->chrom;
+	wi->start = multi->start;
+	wi->finish = multi->finish;
+
+	// Compute means
+	double mean = 0;
+	int groups = multi->count;
+	int index, index2;
+	for (index = 0; index < groups; index++) {
+		Multiplexer * mplx = multi->multis[index];
+		data->means[index] = 0;
+		for (index2 = 0; index < mplx->count; index++) {
+			if (mplx->inplay[index2])
+				data->means[index] += mplx->values[index2];
+			else
+				data->means[index] += mplx->iters[index2]->default_value;
+		}
+		mean += data->means[index];
+		data->means[index] /= data->counts[index];
+	}
+	mean /= data->total_count;
+
+	double inter = 0;
+	double intra = 0;
+	for (index = 0; index < groups; index++) {
+		Multiplexer * mplx = multi->multis[index];
+		inter += mplx->count * (data->means[index] - mean) * (data->means[index] - mean);
+		for (index2 = 0; index < mplx->count; index++) {
+			if (mplx->inplay[index2])
+				intra += (mplx->values[index2] - data->means[index]) * (mplx->values[index2] - data->means[index]);
+			else
+				intra += (mplx->iters[index2]->default_value - data->means[index]) * (mplx->iters[index2]->default_value - data->means[index]);
+		}
+	}
+
+	// F-statistic
+	inter /= groups - 1;
+	intra /= data->total_count - groups;
+	double f = inter / intra;
+
+	// P-value
+	wi->value = 2 * gsl_cdf_fdist_Q(f, multi->count - 1, data->total_count - multi->count);
+
+	// Update inputs
+	popMultiset(multi);
+}
+
+WiggleIterator * FTestReduction(Multiset * multi) {
+	FTestData * data = (FTestData *) calloc(1, sizeof(FTestData));
+	data->multi = multi;
+	data->means = calloc(multi->count, sizeof(double)); 
+	data->counts = calloc(multi->count, sizeof(int)); 
+	int index;
+	for (index = 0; index < multi->count; index++) {
+		data->counts[index] = multi->multis[index]->count;
+		data->total_count += data->counts[index];
+	}
+	return newWiggleIterator(data, &FTestReductionPop, &FTestSeek, NAN);
+}
+
 ////////////////////////////////////////////////////////
 // Mann-Whitney U (Wilcoxon rank-sum test)
 ////////////////////////////////////////////////////////
diff --git a/src/wiggletools.h b/src/wiggletools.h
index dc82ee3..027d37d 100644
--- a/src/wiggletools.h
+++ b/src/wiggletools.h
@@ -89,6 +89,7 @@ Multiset * newMultiset(Multiplexer **, int);
 
 // Reduction operators on sets of sets:
 WiggleIterator * TTestReduction(Multiset *);
+WiggleIterator * FTestReduction(Multiset *);
 WiggleIterator * MWUReduction(Multiset *);
 
 // Output