Only doses of complexed polyriboinosinic: polyribocytidylic acids sufficient to induce interferon, stimulated hyporesponsiveness to re-induction in rabbit kidney cells. Results of experiments designed to delineate the earliest time of appearance of hyporesponsiveness suggested the time of onset was less than i h after the end of a i h exposure to the inducer. The duration of hyporesponsiveness was about 24 h. Interferon itself did not produce hyporesponsiveness. Hence hyporesponsiveness must be related to an event or a substance synthesized before interferon production. The best candidate is a control protein inhibiting interferon production which is rapidly synthesized following exposure to an inducer.