The importance of epistasis-non-additive interactions between alleles-in shaping population fitness has long been a controversial topic, hampered in part by lack of empirical evidence(1-4). Traditionally, epistasis is inferred on the basis of non-independence of genotypic values between loci for a given trait. However, epistasis for fitness should also have a genomic footprint(5-7). To capture this signal, we have developed a simple approach that relies on detecting genotype ratio distortion as a sign of epistasis, and we apply this method to a large panel of Drosophila melanogaster recombinant inbred lines(8,9). Here we confirm experimentally that instances of genotype ratio distortion represent loci with epistatic fitness effects; we conservatively estimate that any two haploid genomes in this study are expected to harbour 1.15 pairs of epistatically interacting alleles. This observation has important implications for speciation genetics, as it indicates that the raw material to drive reproductive isolation is segregating contemporaneously within species and does not necessarily require, as proposed by the Dobzhansky-Muller model, the emergence of incompatible mutations independently derived and fixed in allopatry. The relevance of our result extends beyond speciation, as it demonstrates that epistasis is widespread but that it may often go undetected owing to lack of statistical power or lack of genome-wide scope of the experiments.