The chemopreventive effects of beta-carotene and 13-cis-retinoic acid (RA) on chemically induced salivary gland tumors were studied in rats. Young male Sprague-Dawley rats were injected in one of the submandibular salivary glands with 1 mg of dimethylbenzanthracene (DMBA) dissolved in olive oil. The contralateral gland was injected with the vehicle alone. Rats were divided into four groups and were fed ad libitum a semisynthetic diet supplemented with 0 or 100 mg beta-carotene/kg diet, or 20 or 100 mg RA/kg diet. Rats were killed at 22 weeks after the DMBA treatment, and tumors were examined histologically. Tumors were generally found to be squamous cell carcinomas or poorly differentiated neoplasms resembling squamous cell carcinomas. The tumor incidence was slightly lower in rats fed the diet supplemented with beta-carotene. RA had no appreciable effect on tumor incidence. A high activity of gamma-glutamyl transpeptidase was histochemically demonstrated in the tumors. There were some mortalities in the beta-carotene and RA supplemented groups, especially in the group fed high levels of RA. This mortality appeared to be related to vitamin K becoming somewhat limited.