The action of TSH on the process of iodide organification was studied in rat thyroid glands under different experimental in vitro incubation conditions. The effects on glands of both short and prolonged exposure to TSH were evaluated using two different procedures: continuous and pulse labelling of thyroids with radioactive iodide. It was demonstrated that during prolonged contact with thyroid cells, TSH stimulates iodide organification periodically. This periodic effect is cyclic and is composed of a stimulatory and an inhibitory phase. Each cycle lasts 30-45 min, and several cycles follow one another in a regular manner. Furthermore, it has been shown that the periodic effect of THS is due to an intrinsic property of the thyroid cell to respond in a cyclic manner to hormonal stimulation. TSH stimulated the accumulation of organic iodide only when introduced at a precise phase of the cycle. The same type of discontinuous thyroid cell response was obtained when TSH was replaced by its intracellular mediator, cAMP. This indicates that the initiation of the cyclic response to hormonal stimulation is localized at the steps after that of cAMP formation. It seems, therefore, that this cyclic response of thyroid glands is not related to the recently observed phenomenon of desensitization. This phenomenon, characterized by the development of resistance in many target organs and cells toward their respective hormonal stimulators, is due to modifications in steps preceding those of cAMP formation. The discontinuity of thyroid gland response to both TSH and cAMP described in this work seems to be a new phenomenon, whose physiological significance and possible molecular mechanisms are discussed.