A chronic toxicity and carcinogenicity study, in which male and female F344/DuCrj rats were given potassium iodide (KI) in the drinking water at concentrations of 0, 10, 100 or 1000 ppm for 104 weeks, and a two-stage carcinogenicity study of application at 0 or 1000 ppm for 83 weeks following a single injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN), were conducted. In the former, squamous cell carcinomas were induced in the salivary glands of the 1000 ppm group, but no tumors were observed in the thyroid. In the two-stage carcinogenicity study, thyroidal weights and the incidence of thyroid tumors derived from the follicular epithelium were significantly increased in the DHPN+KI as compared with the DHPN alone group. The results of our studies suggest that excess KI has a thyroid tumor-promoting effect, but KI per se does not induce thyroid tumors in rats. In the salivary gland, KI was suggested to have carcinogenic potential via an epigenetic mechanism, only active at a high dose.