The importance of autonomic nervous activity for the pancreatic hormonal response to exercise in man was studied. 7 men ran at 58% of V(O2)max (determined without administration of drugs) to exhaustion during alpha-adrenergic blockade with phentolamine (P), during parasympathetic blockade with atropine (A), or without drugs (C). At rest phentolamine increased the plasma concentrations of both insulin and norepinephrine. During exercise norepinephrine concentrations increased and were in P experiments 3 times the concentrations in C experiments. Insulin always declined during exercise but in P experiments never decreased below basal levels. At identical times neither glucagon nor glucose differed significantly in the different expts. Thus during exercise alpha-adrenergic blockade increased insulin concentrations but did not diminish the glucagon response. Nor was this response increased when beta-receptor stimulation in P experiments was intensified by the particularly high catecholamine concentrations. The concentrations of FFA, glycerol and lactate were highest in P experiments and identical in A and C experiments. These findings indicate that during prolonged moderate exercise in man insulin secretion is depressed by stimulation of alpha-adrenergic receptors whereas glucagon secretion is not influenced by adrenergic receptors. Stimulation of beta-adrenergic receptors enhances lipolysis but neither lipolysis nor pancreatic hormonal secretion is influenced by cholinergic activity during exercise.