The effect of treatment with indomethacin on methylazoxymethanol-induced rat large bowel carcinomas was investigated. Eight-week-old male Donryu rats received an intraperitoneal injection of 20 mg/kg body weight of methylazoxymethanol acetate once a week for 6 weeks. Fifteen rats were sacrificed at the 25th week. It was confirmed that the incidence of large bowel tumors (adenocarcinomas) was 60% and the mean number of tumors per tumor-bearing rat was 2.0. The other rats (23 approximately 30 rats in each group) were given the treatment with an intrarectal instillation of 7.5 mg/kg body weight of indomethacin, 7.5 mg/kg of hydrocortisone, 75 mg/kg of PS-K, vehicle alone, or non-treatment daily from the 27th to 29th week. All of these rats were sacrificed at the 30th week. The tumor incidence was 50% or 55% in indomethacin- or hydrocortisone-treated rats. It was significantly lower than 83% or 87% of the rats treated wih PS-K or vehicle, or untreated. The mean number of tumors was also smaller in those 2 groups of rats (2.0 or 2.1 tumors) than in 3 groups (3.5 or 3.3 tumors). The results demonstrated that the intrarectal dose of indomethacin and hydrocortisone inhibited the development of tumors from microscopic carcinoma lesions in the large bowel and growing further. It seems that indomethacin might be effective to treat the early stage disease with relatively small number of growing tumor cells.