The effects of treatment with naturally occurring antioxidants, selenium, beta-carotene, ferulic acid, esculin and eugenol during the promotional phase of tumor development were investigated in male F344 rats pre-treated with 1,2-dimethylhydrazine (DMH) and 1-methyl-1-nitrosourea (MNU). Animals were given 3 subcutaneous injections of DMH at a dose of 40 mg/kg body wt. within 1 week and then were injected with MNU i.p. at a dose of 20 mg/kg body wt. 2 times per week, for 2 weeks. Thereafter, the rats were maintained on diet containing either 0.2% beta-carotene, 2 ppm selenium, 1% ferulic acid, 1% esculin or 0.8% eugenol. At week 52, surviving rats were killed and complete histological examinations were performed. Administration of eugenol enhanced the development of both hyperplasia and papillomas in the forestomach. Although treatment with beta-carotene tended to decrease the incidence and number of large intestinal carcinomas, beta-carotene, selenium, esculin and eugenol all decreased the incidence of kidney nephroblastomas, the differences were not statistically significant. The results thus showed that eugenol exerts promoting activity for forestomach carcinogenesis while the other antioxidants might have weak organ-specific inhibitory effects under these experimental conditions.