The Abdominal B (AbdB) genes constitute a distinct subfamily of homeobox genes that exhibit posterior domains of expression, including the genital imaginal disc in Drosophila and the developing urogenital system in vertebrates. We have mutated the AbdB gene Hoxa10 in mice. We report here that homozygotes are fully viable and show an anterior homeotic transformation of lumbar vertebrae. All male homozygotes manifest bilateral cryptorchidism resulting in severe defects in spermatogenesis and increasing sterility with age. Female homozygotes ovulate normally, but about 80% are sterile because of death of embryos between days 2.5 and 3.5 post coitum. This coincides spatially and temporally with expression of maternal Hoxa10 in distal oviductal and uterine epithelium. These results indicate a role for AbdB Hox genes in male and female fertility and suggest that maternal Hoxa10 is required to regulate the expression of a factor that affects the viability of preimplantation embryos.