Cardiac catheterization studies, performed 3 weeks after cardiac homotransplantation, revealed nearly normal cardiac performance. Alteration in heart rate by right atrial pacing, passive elevation of the legs, and exercise modified cardiac performance predominantly by variation in ventricular filling. Isoproterenol infusion increased stroke volume above the level predicted from the ventricular end-diastolic pressure. The heart was hypersensitive to beta-adrenergic stimulation with isoproterenol as judged by a greater responsiveness of the donor sinus node than the recipient sinus node, by prolongation of ventricular filling time, and by shortening the P-R interval for any given paced heart rate. These measures permitted tests for endogenous catecholamine effects during passive leg elevation and during exercise. Only after the 3 minutes of exercise was a small beta-adrenergic effect detectable. These data demonstrate the dependence of the denervated human heart upon variation in ventricular filling as the predominant mode of regulation of cardiac performance.