Cardiac catheterization studies were performed in eight patients 1 year after cardiac transplantation and in two of these again at 2 years. Intracardiac pressures at rest were normal in all patients, both 1 and 2 years postoperatively. Average cardiac index at rest at 1 year was 2.3 liters/min/m2and average heart rate was 90 beats/min. Responses to amyl nitrite, atropine, and tyramine failed to demonstrate efferent autonomic reinnervation of the donor hearts. Findings associated with a 10-min period of submaximal supine bicycle exercise 1 year after transplantation included: (1) a gradual rise in heart rate throughout most of the exercise period; (2) prompt elevation of left ventricular end-diastolic pressure by an average increment of 10 mm Hg, followed by a decrease during late exercise in some patients; (3) a progressive increase in LV systolic pressure throughout the first half of the exercise period; (4) a continuously positive change in LV rate of pressure change (dp/dt) throughout exercise; (5) an average 44% increase in stroke volume; and (6) an average 92% increase in cardiac output. The slope of the regression of cardiac output on oxygen uptake during exercise was within the range of normal. Cardiac output, however, was lower than normal both at rest and during exercise, and the arteriovenous oxygen diflerence was accordingly widened.In one patient studied 1 and 2 years after transplantation, hemodynamic findings were comparable on both occasions. In the other, however, the cardiac output response to exercise was distinctly diminished at 2 years as compared to 1 year, due almost entirely to failure of the stroke volume to increase. Coronary arteriography in this recipient revealed evidence of occlusive coronary disease compatible with graft atherosclerosis.These studies demonstrate the sustained capacity of the transplanted human heart to support normal physical activity late in the postoperative period. Although utilizing atypical adaptive mechanisms characteristic of the denervated heart, the transplanted heart responds in a directionally appropriate manner to the metabolic demands of exercise.