It is unknown whether the non-transplanted, denervated human heart is supersensitive to beta-adrenergic agonist in terms of inotropism and chronotropism. In the present study, 36 patients with normal left ventricular (LV) wall motion were divided into 3 groups according to the cardiac metaiodobenzylguanidine (MIBG) scintigrams: group I with normal MIBG uptake, group II with regionally reduced MIBG uptake, and group III with globally reduced MIBG uptake (heart-to-mediastinum ratio <1.6). Before isoproterenol (IP) infusion, heart rate (HR), blood pressure (BP) and echocardiographic indices were similar among the groups. There was a trend toward a greater increase in HR with IP (0.01 microg x kg (-1) x min(-1)) in group III (27+/-18 beats/min) than in groups I (20+/-8) and II (17+/-8) despite the lack of a significant difference in BP reduction by IP. During IP infusion, increases in posterior wall motion amplitude and LV fractional shortening were significantly greater in group III (4.5+/-1.8 mm and 16.4+/-5.4%, respectively) than in groups I (1.5+/-2.5 mm and 8.7+/-6.4%) and II (2.6+/-1.7 mm and 8.9+/-7.9%). The present results suggest that the sympathetically denervated human heart is supersensitive to IP and the exaggerated responses may be caused, at least in part, by a postsynaptic mechanism.