The effects of the administration of insulin on plasma free fatty acid (FFA) levels of adrenalectomized and sham-operated (SO) chickens were compared in order to determine if the lipid-mobilizing action of the hormone is mediated by the adrenal glands. Plasma FFA levels of adrenalectomized and SO chickens were the same before hormone administration (0.69 +/- 0.03 vs 0.72 +/- 0.03 mu Eq/ml, N = 15 for each group). Injection of insulin (1 U/kg, iv) caused a significant increase of plasma FFA of SO chickens (103%) but did not modify FFA levels of adrenalectomized chickens. Blood sugar levels were higher in SO than adrenalectomized birds (163 +/- 4 vs 126 +/- 3 mg/100 ml, N = 9 for each group) before insulin administration but the magnitude of the reduction of blood sugar induced by insulin was similar for both groups. The marked lipolytic effect of glucagon (0.2 mg/kg, iv) on intact chickens was affected only to a small extent by adrenalectomy but, in contrast, the blood sugar response to glucagon was greatly reduced (27%) in adrenalectomized chickens. Significant increases (38%) in plasma FFA levels of intact chickens were obtained during the first few hours after a single intravenous injection of hydrocortisone (10 mg/kg, iv). The data show that the presence of the adrenal glands is essential for the increase in plasma FFA induced by insulin in chickens, and suggest that the lipid-mobilizing effect of the hormone in this species is due to an increased secretion of endogenous glucocorticoids following insulin-induced hypoglycemia.