Exercise has an anxiolytic activity and it increases the concentrations of atrial natriuretic peptide (ANP). Because ANP has an anxiolytic activity, this hormone might contribute to the anxiolytic effects of aerobic exercise. Cholecystokinin-tetrapeptide (CCK-4)-induced panic attacks were studied in 10 healthy subjects after "quiet rest" or 30 min of aerobic exercise. Plasma ANP concentrations were measured before and after exercise or quiet rest using a commercial IRMA kit. Compared to quiet rest, CCK-4-induced anxiety was reduced and plasma ANP concentrations were increased by prior exercise. This anxiolytic activity of exercise was correlated with the increase in plasma ANP concentrations. Our results suggest that besides other mechanisms, ANP might be a physiologically relevant humoral link between the heart and anxiety-related behavior contributing to the acute anxiolytic effects of exercise.