N-Methyldopamine (epinine), one of the few modifications of the dopamine (DA) molecule that retains agonist activity at the DA, receptor, was administered orally as the diisobutyric ester, ibopamine (100, 200, and 300 mg), to 15 patients with congestive heart failure. An increase in cardiac index and decline in systemic vascular resistance was observed with each dose, and these hemodynamic effects persisted for 3 to 6 hr. Small transient increments in right atrial and pulmonary capillary wedge pressures occurred 0.5 hr after ingestion of 200 and 300 mg of ibopamine, but these pressures returned to baseline or lower levels within 30 min. Heart rate and mean arterial pressure were unchanged. Plasma concentrations of epinine peaked 0.5 hr after administration of drug and then declined to minimal levels at 3 hr. Ten patients enrolled in a trial to evaluate the efficacy of long-term therapy with ibopamine; after 8 weeks of treatment, the initial hemodynamic responses to the drug were attenuated and no significant improvement in oxygen uptake at peak exercise was observed. A decline in plasma norepinephrine concentrations, which could be attributed to activation of a2-adrenoceptors and/or DA2 receptors on sympathetic nerves, was observed after initial administration of ibopamine and persisted after long-term drug ingestion; no long-term hemodynamic benefit could be ascribed to the reduction in sympathetic activity. Circulation 73, No. 4, 740-748, 1986. THE ADMINISTRATION of dopamine to patients with congestive heart failure may effect an improvement in the performance of the impaired myocardium, and thus an oral formulation of this drug would be desirable. 2 The beneficial actions of dopamine in patients with heart failure have been attributed not only to a positive inotropic effect that is mediated by activation of the 8,1-adrenoceptor, but also to its agonist activity at the dopamine vascular (DA1) receptor.3 Activation of the DA1 receptor in the renal vascular bed appears primarily responsible for the marked natriuresis produced by this drug. N-Methyldopamine (epinine) is one of the few modifications of the dopamine molecule that retains full agonist activity at the DA1 receptor.4 Ibopamine is the diisobutyric ester of epinine, and after ingestion, it is hydrolyzed by plasma esterases to yield epinine.5 Initial studies have demonstrated beneficial short-term hemodynamic responses to ibopamine in patients with heart failure.-9 This investigation was undertaken to evaluate the hemodynamic actions and bioavailability of ibopamine after short-and long-term administration to patients with chronic congestive heart failure, and to assess the role of the sympathetic nervous system in modulating the hemodynamic responses to the drug.