A denervated heart coupled to a periphery previously exposed to high catecholamine levels provides a unique model to study adrenoceptor physiology. Six orthotopic transplant patients (1.3 +/- 0.8 years postoperative) were age matched with six atropine-treated normal subjects. Simultaneous two-dimensionally targeted left ventricular echo-cardiograms and calibrated carotid pulse tracings were recorded. Left ventricular contractility was assessed with use of heart rate- and load-independent end-systolic indexes. Studies were performed at baseline and during dobutamine infusion with and without beta-adrenergic blockade with use of propranolol; effects were assessed during afterload changes generated by the alpha 1 agonist methoxamine. There were no differences in baseline contractility or reserve between transplant patients and normal subjects. The heart rate response to dobutamine was greater for transplant patients (p less than 0.001). In both groups, the positive inotropic and chronotropic effects of dobutamine were ablated by propranolol. Dobutamine plus propranolol (unopposed alpha 1 effect) did not change mean systemic pressure in transplant patients while markedly raising mean systemic pressures in normal subjects (36 +/- 18 mm Hg; p less than 0.001). In addition, during initial challenge with methoxamine, the transplant patients required 60% more alpha 1 agonist than did the normal subjects (p less than 0.001) to obtain a pressor effect. In summary, transplant patients who were previously in severe heart failure have normal left ventricular inotropic response to beta 1 activation and blockade, exaggerated chronotropic response to dobutamine and reduced sensitivity to stimulation with alpha 1-adrenoceptor agonists. These findings are consistent with a differential response of adrenoceptors to long-term stimulation after cardiac transplantation.