We have previously shown that adrenodemedullation combined with chemical sympathectomy decreases the exercise-induced muscular glycogen breakdown in rats. Now we have elucidated to what extent the effect of combined adrenodemedullation and sympathectomy can be ascribed to the lack of either the adrenal medulla or of the peripheral sympathetic nerve endings. Rats were either adrenodemedullated or underwent sham operation and subsequent unilateral hindleg sympathectomy. Three weeks after adrenodemedullation and 1 wk after sympathectomy, the rats either rested or swam with a tail weight for 75 min or continued swimming to exhaustion. The exercise-induced muscular glycogenolysis was markedly impeded by adrenodemedullation but not by sympathectomy. During the first 75 min of exercise, hepatic glycogenolysis was decreased in adrenodemedullated rats compared with sham-operated rats, and blood glucose only increased in the latter. At exhaustion, plasma insulin and glucagon were higher and lower, respectively, in adrenodemedullated rats than in sham-operated rats, whereas blood glucose did not differ significantly between these groups. During prolonged swimming in rats, adrenomedullary hormones enhance muscular glycogenolysis, glucagon secretion, and the early hepatic glycogenolysis but inhibit insulin secretion.