It is believed that a combination of environmental factors with mutagens induces carcinomas derived from thyroid follicular cells. In this study we tried to ascertain whether a single short-term exposure to external radiation is sufficient to induce thyroid carcinomas in rats under long-term high or low dietary iodine intake. Rats were tested over a period of 110 wk under high (approximately 10-fold of normal), normal, and low (approximately 0.1-fold of normal) daily iodine intake. Forty-day-old animals were subjected to single external radiation of 4 Gy or sham radiation. Thyroid function was tested weekly, and thyroid morphology was determined after 15, 35, 55, and 110 wk. Iodine deficiency, but not high iodine intake, led to a decrease in T(3) and T(4) plasma levels, but to an increase in TSH, which became significant after 9 and 11 wk of treatment, respectively. Both high and low iodine treatment significantly increased the proliferation rate and induced thyroid adenomas, but no malignancies after 55 and 110 wk. Radiation with 4 Gy resulted in a significant destruction of the follicular structure. Under high and low iodine intakes (50-80% of animals), but not under normal iodine supply, thyroid carcinomas were observed in irradiated rats. Thus, the increased proliferation rate induced under the experimental conditions described in this study is apparently not sufficient to cause thyroid carcinomas, but the presence of a mutagen-like radiation is required. This model may help to define genetic alterations long before histological changes are detectable.