Hormonal manipulation has been proposed as a possible new approach to the treatment of pancreatic cancer. We studied the effect of orchiectomy and testosterone replacement on early stage pancreatic carcinogenesis induced by diisopropanolnitrosamine (DIPIN) in Syrian golden hamsters. Eighty-five hamsters (mean body weight, 100 g) were divided into the following treatment groups: 1) DIPN (n = 20); 2) DIPN plus orchiectomy (n = 17); 3) DIPN plus orchiectomy plus testosterone (n = 18); 4) orchiectomy (n = 10); 5) sham operation (n = 10); 6) DIPN plus testosterone (n = 10). DIPN (125 mg/kg/body wt.) was administered s.c. every week and testosterone propionate (10 micrograms/g) was administered s.c. every 3 weeks. Bilateral orchiectomy was performed 1 week after the first injection of DIPN. All animals were killed 15 weeks after starting the treatment. The whole pancreas was removed, weighted and histologically examined. There was no difference in the incidence of preneoplastic lesions among groups 1, 2, 3 and 6 (respectively 87%, 83%, 77% and 80%); 3 animals in each group developed invasive carcinoma. In control groups (4 and 5), no precancerous lesions were recorded. In this experimental model, orchiectomy and testosterone replacement had no effect on nitrosamine-induced pancreatic carcinogenesis.