To examine whether beta-adrenergic desensitization occurs after prolonged exercise, echocardiograms, heart rate responses to isoproterenol, plasma catecholamines, and circulating lymphocyte beta-adrenergic receptors were examined in 10 sedentary normal subjects at rest and after brief (10 min) and exhaustive (mean duration 95 min) cycle exercise. Resting end-diastolic volume and ejection fraction were significantly reduced after exercise (from 120 +/- 34 to 100 +/- 26 ml and from 60 +/- 0.4 to 54 +/- 0.6%, respectively; both P < 0.05). The amount of isoproterenol needed to increase heart rate 15 and 25 beats/min increased in a dose- (exercise duration) related fashion, and the increase in amount of isoproterenol needed after prolonged exercise was closely related to the decrease in ejection fraction (r2 = 0.67, P = 0.004). Circulating lymphocyte beta-receptor density and affinity, agonist binding, and adenylylcyclase levels were unchanged with prolonged exercise. In conclusion, prolonged exercise in sedentary normal subjects resulted in reduced cardiac chronotropic responsiveness to isoproterenol that was not reflected in peripheral lymphocyte beta-adrenergic-receptor downregulation.