The relative accumulation of [alpha]-aminoisobutyrate (AIB) in diaphragm and gastrocnemius muscle of intact, hypophysectomized (2 day) and adrenalectomized (6 day) rats has been examined in vivo with respect to the effect of insulin alone, and in adrenalectomized rats of insulin in conjunction with epinephrine and corticoids. Adrenalectomy, but not hypophysectomy, reduces the ability of insulin to elevate the accumulation of AIB in muscle to the level observed after insulin in intact rats; e. g., AIB distribution values obtained after insulin in diaphragm were 194% in adrenalectomized, and 385% and 420% in intact and hypophysectomized rats, respectively. Epinephrine alone has slight effect on muscle AIB in adrenalectomized rats, but concurrent administration of epinephrine and insulin to adrenalectomized rats restores AIB distribution nearly to the level observed in adrenal-intact rats receiving insulin. Administration of 0.8 mg of either deoxy-corticosterone (DOCA) or cortisol each day over the interval between adrenalectomy and sacrifice resulted in normal AIB distributions in diaphragm; both corticoids, especially DOCA, also enhance the AIB accumulation response to insulin. Acute corticoid administration did not augment the response to insulin. Considering that epinephrine and insulin were found to reduce plasma [K+], and that corticoids, especially DOCA, have a similar effect, the suggestion emerges that these hormonal effects on AIB accumulation may be related to alterations in electrolyte metabolism. Irrespective of this possibility, epinephrine and corticoids appear to independently play supportive roles in the response of muscle to insulin with respect to AIB transport.