Eggs of Rana clamitans in their own jelly coat are not fertilized by sperm of other species. When the eggs were surrounded by jelly from another species, they were fertilized by R. catesbeiana and R. septentrionalis sperm. The hybrid nature of the resulting embryos was confirmed by detection of paternal enzyme forms. The R. clamitans female times R. septentrionalis male embryos arrested by the tailbud stage. The R. clamitans female times R. catesbeiana male embryos developed into viable tadpoles and subsequently metamorphosed. The hybridization results coupled with the similarity of enzyme patterns indicate that R. clamitans and R. catesbeiana are genetically closely related. R. clamitans is probably not as closely related to R. septentrionalis based on the enzyme patterns. Since cross-fertilization or early developmental failures of hybrids could be explained by a small number of genes, such failures must be considered with caution in determining species relationships.