Reproductive isolation between biological species is characterized by Haldane's rule, which states that the heterogametic sex (XY or ZW) suffers the most dysfunctional effects of hybridization. It has been hypothesized that, in addition to X-linked recessive genes, Haldane's rule also reflects the faster evolution of genes related to male reproduction (faster-male evolution). We used sex-reversed hybrid Xenopus to test faster-male evolution by examining the fertility of sex-reversed individuals with the genotype of the inverse phenotypic sex. Hybrid males are sterile and hybrid females are fertile irrespective of their genotypic sex. Gene expression profiles match these adult phenotypes, and our results demonstrate that faster-male evolution is the most likely mechanism producing hybrid male sterility.