Experiments were conducted to determine whether gamma-ray-induced genetic damage in parental rats can lead to the development of cancer in their offspring rats using glutathione S-transferase-positive (GST-P+) hepatic foci with or without the addition of diethylnitrosamine (DEN), a carcinogen. A single 1 Gy whole-body exposure of gamma-rays was given to pregnant rats at day 14 and during postnatal week 3, DEN was intraperitoneally injected twice in 1 week. Female pups from irradiated maternal and paternal rats were also used. Twelve weeks after birth, the rats were sacrificed. GST-P+ foci in animals subjected only to radiation were not different to those of normal control pups, but the incidence of GST-P+ foci was 2.4 times higher in pups treated with DEN alone at 3 weeks after birth than in those irradiated after the onset of pregnancy. In DEN-combined groups, irradiation of post-pregnant or maternal and paternal rats with gamma-rays before mating significantly increased both the incidence and area of GST-P+ foci when compared to those of rats treated with DEN alone. The proliferating cell nuclear antigen (PCNA) labeling index was significantly higher in the offspring of rats subjected to radiation alone or radiation combined with DEN than in normal control pups. Using a rat-liver model, the results of this study indicate that although the dose did not induce phenotypic malformation, exposure to radiation during the embryonic or pre-embryonic stage increases susceptibility to carcinogens.