In order to verify the existence of a "short-loop" negative feedback between iodothyronines and adenylate cyclase system of human thyroid, we have studied the effect of preincubation with iodothyronines, iodotyrosines, iodothyronine analogues and iodide on TSH-induced cAMP cellular accumulation in normal human thyroid cells in primary culture. Iodide did not produce an inhibitory effect on TSH-dependent adenylate cyclase system both in normal human thyroid plasma membranes and cultured cells. Iodothyronines at a 30-40 microM concentration did not inhibit the TSH-dependent adenylate cyclase activity of human thyroid plasma membranes; however at a 1 microM concentration they were able to inhibit the TSH-dependent cAMP accumulation by cultured cells. Preincubation with iodotyrosines and iodothyronine analogues failed to inhibit the TSH-responsive cAMP accumulation in human thyroid cultured cells.