The effects of sex hormones on the induction of gastric carcinoma by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in Wistar rats. Well-differentiated adenocarcinomas developed with high frequency (88%) on the glandular stomach of male rats given MNNG in drinking water (50 micrograms/ml) for 4 months and sacrificed on the 12th month of the experiment. In female rats given MNNG, no gastric cancer was observed. In the castrated or estradiol-treated male rats, the incidence of carcinoma was lower (29 and 68%, respectively) than in the nontreated male rats. Histologically, poorly differentiated adenocarcinomas were observed more frequently in these groups than in the nontreated male group. In MNNG carcinogenesis, female, castrated male and estrogen-treated male rats had a lower incidence of gastric cancer with lower histological differentiation than did nontreated male rats.