In hypophysectomized rats given dietary regimens either rich or deficient in iodine, the increase in thyroid cyclic AMP concentration induced acutely by a single dose of TSH was significantly less in iodine-enriched than in iodine-deficient animals. Direct assays revealed that this difference was because the thyroid adenylate cyclase response to TSH was less in the iodine-enriched animals, phosphodiesterase activity being no different in the two groups. This effect may explain the inhibitory action of dietary iodine enrichment on diverse functional and anatomical responses of the thyroid to TSH.