In order to compare ibopamine (IBO), a dopamine congener, with isosorbide mononitrate (ISMN) and to study their interaction in effects on the capacitance vasculature in congestive heart failure (CHF), a prospective, randomized, placebo-controlled, double-blind clinical trial was performed in 32 patients with New York Heart Association class II-IV CHF, randomly assigned to receive single oral doses of placebo, 200 mg IBO, 20 mg ISMN, or both IBO and ISMN. After labelling of red cells with 99mTc, changes in regional radioactivity, indicative of changes in blood volume, were recorded using a γ-camera before and at 30, 60 and 120 min after drug administration. At 30 and 60 min, arterial systolic and pulse pressures were higher with IBO than with ISMN and placebo (for pulse pressure by mean 13.7 mm Hg, 95% confidence interval 4.5-23.0 mm Hg, at 30 min), probably reflecting an IBO-induced rise in stroke volume at unchanged heart rate and mean arterial pressure. IBO did not change regional radioactivity except for a transient increase of 4.4% (0.5-7.6%) in the thorax at 30 min. This was attenuated by concomitant ISMN treatment since, starting at 30 min, the drug increased radioactivity in the legs, compared with patients not receiving the drug, by 8.0% (95% confidence interval 0.2-15.8%), leading to a fall in thoracic and left ventricular radioactivity at 30 min of 3.4% (0.3-7.0%) and 6.4% (0.8-11.9%), respectively, and a fall of 5.5% (0.5-10.5%) in hepatic radioactivity at 60 min. In CHF, arterial vasodilating IBO lacks a peripheral venodilating effect and even transiently increases thoracic blood volume, caused probably by a transient rise in left ventricular afterload. This is attenuated by ISMN, which acutely unloads the left ventricle, thorax and liver by venodilation in extremities.