In an attempt to induce a high incidence of prostate carcinoma, N-methylnitrosourea (MNU), a multipotential carcinogen, was given during the period of cell proliferation of the prostate gland induced by administration of methyltestosterone (MT) to F344 rats pretreated with ethinyl estradiol (EE). Rats were given diet containing EE for 3 weeks and then diet containing 300 ppm of MT for 5 days. On the 3rd day of MT-treatment, they were given a single intravenous injection of 50 mg/kg body wt. of MNU. Control rats (group 4) were given vehicle only. After treatment with MT for 5 days, the rats were given basal diet (group 1), diet containing MT (group 2) or diet periodically containing EE (groups 3 and 4) until the end of the experiment (week 60). Carcinoma of the prostate was found only in 1 of 17 rats in group 3. Atypical hyperplasia of the prostate was found in 1 of 10 rats in group 1 and 3 of 17 rats in group 2. The incidences of atypical hyperplasia of the seminal vesicles in groups 1-3 were 0%, 41% and 29%, respectively. No tumor promoting effect of MT or EE was observed except promotion by MT on the development of atypical hyperplasia of the seminal vesicles.