The genes causing postzygotic isolation in two Drosophila hybridizations were localized to regions of the X chromosome. The X has a large effect on D. pseudoobscura pseudoobscura ("U.S.A.")-D. pseudoobscura bogotana ("Bogota") hybrid male sterility. Recombination analysis shows that this effect is due entirely to a small chromosome region representing less than 20 per cent of the X. This result suggests that a single X-linked gene may be involved. A maximum likelihood mapping procedure places this hybrid sterility gene at position 50.3 (95 per cent limits = 46.9-54.4). Analysis also shows that this putative gene has a very large effect on hybrid fitness: substitution of a Bogota for a U.S.A. allele almost halves hybrid male fertility. The X-chromosome also has a large effect on male and female sterility in the D. pseudoobscura-D. persimilis hybridization. Male sterility in this cross appears to involve more X-linked genes than in the younger U.S.A.-Bogota hybridization: genes on both arms of the X are involved. Sterility of females, however, is caused by gene(s) restricted to the left arm of the X. Thus male and female sterility in this hybridization must involve some different loci. This result militates against the traditional explanation of Haldane's rule.