Postzygotic reproductive isolation is characterized by two striking empirical patterns. The first is Haldane''s rulethe preferential
inviability or sterility of species hybrids of the heterogametic (XY) sex. The second is the so-called large X effectsubstitution of one species''s X chromosome for another''s has a disproportionately large effect on hybrid fitness compared to similar substitution of an autosome. Although the first rule has been well-established, the second rule remains controversial. Here, we dissect the genetic causes of these two rules using a genome-wide introgression analysis of Drosophila mauritiana chromosome segments in an otherwise D. sechellia genetic background. We find that recessive hybrid
incompatibilities outnumber dominant ones and that hybrid male steriles outnumber all other types of incompatibility, consistent with the dominance and faster-male theories of Haldane''s rule, respectively. We also find that, although X-linked and autosomal
introgressions are of similar size, most X-linked introgressions cause hybrid male sterility (60) whereas few autosomal introgressions do (18). Our results thus confirm the large X effect and identify its proximate cause: incompatibilities causing hybrid male sterility have a higher density on the X chromosome than on the autosomes. We evaluate several hypotheses for the evolutionary cause of this excess of X-linked hybrid male sterility.