The effects of high-fat diets on the spontaneous occurrence of uterine endometrial adenocarcinomas were examined in the Donryu rat. Ninety females at 6 weeks of age were equally divided into 3 groups. Animals in group 1 were fed a basal diet, while those in groups 2 and 3 received powdered basal diets containing 10% and 20% corn oil until 15 months of age, when all survivors were sacrificed. For sequential serum steroid assay and histological examination of sex organs, additional rats were fed diets containing 20% corn oil or without supplement. Body weight gain in group 3 was significantly increased, while in group 2 it was similar to that in the control. In both high-fat groups, calorie intake and weight of fat deposits in the abdominal cavity were significantly increased. The incidences of uterine adenocarcinomas in groups 2 and 3 were 18% (P < 0.05) and 7%, respectively, as compared to 0% in group 1. Severe hyperplasia (hyperplasia+++) also showed a non-significant tendency for increase in incidence. In both high-fat groups, an elevated incidence of persistent estrus was generally observed until 8 months of age. Sequential assays of steroid hormones in rats fed a 20% fat diet showed a tendency for early elevation and continued high values for the serum estrogen: progesterone (E2:P) ratio. In these rats, histological changes in the ovary, uterus, and vagina also appeared at an early stage, as compared to rats fed the basal diet. These results suggest that a high-fat diet may exert a slight promoting effect on the spontaneous occurrence of uterine adenocarcinomas in Donryu rats, and this might be mechanistically related to hormonal imbalance and a high E2:P ratio in particular.