The autosomal dominant mutant gene, tail anomaly lethal (Tal), of the rat is lethal when homozygous but affects tail morphology (kinks and reduced length) and body weight when heterozygous. There is no apparent sex effect on the expression of Tal. It is incompletely penetrant; has variable expressivity, which is influenced partly by its genetic background; and is not linked to the major histocompatibility complex (MHC). The heterozygous Tal gene and the homozygous grc genes, which are linked to the MHC and affect body size and fertility, interact to cause intrauterine death at a time between implantation (five to seven days post-fertilization) and 15 days of gestation. This interaction shifts the time of death from the immediate postnatal period when the homozygous grc genes act to the time during gestation when the homozygous Tal gene would cause death. This description of lethal epistatic interaction in the rat appears to be the first report of this phenomenon in mammals.