Eleven thyroid follicular adenomas, cold on scintigram were analysed to determine whether defect in iodide organification or iodide transport causes low iodide uptake in cold nodules of the thyroid. The results were compared with perinodular tissue samples used as controls. In eight of eleven adenomas incubated in medium with 0.1 microM of iodide, newly organified iodide was 85.6 +/- 8.6% of total trapped iodide, which was significantly higher than 52.3 +/- 12.8% in controls. The remaining three adenomas showed a value as low as 4.0 +/- 2.7%. These data suggest that follicular adenomas are of two different groups; one with high organic iodinating activity and the other with none. These two groups were defined as FA-1 and FA-2. Thyroid:medium ratios of iodide of both groups were significantly depressed, indicating that the essential alteration in the thyroid follicular adenoma is a disturbance of iodide transport. In contrast to controls of organification of iodide was not inhibited by the addition of 100 microM iodide to the medium in FA-1 adenomas. In both FA-1 and FA-2, the degree of iodination of thyroglobulin (Tg) in equilibrium was significantly lower than that in controls. Therefore, in most cases with the follicular adenoma, the principal cause of decreased iodination of Tg was considered to be a depressed iodide transport, but not an impairment of organic iodination.