Four studies were conducted in 36 patients with severe chronic heart failure to compare the central hemodynamic effects of captopril (CPT) to other vasodilator agents. While CPT produced less marked increases in cardiac output than did hydralazine (n = 14), nitroprusside (n = 15), or prazosin (n = 7), it produced decreases in left ventricular filling pressures similar to nitroprusside and prazosin but more than hydralazine. CPT and isosorbide dinitrate (n = 11) produced similar decreases in systemic vascular resistance and left ventricular filling pressure. However, cardiac output increased less with CPT than with nitrates, because heart rate slowed during CPT therapy. In addition, mean right atrial pressure decreased less with CPT than with nitrates, because CPT had minimal effects on limb venous capacitance and pulmonary arteriolar resistance. Alterations in left ventricular pressure-volume relationships likely contributed to the marked decreases in left ventricular filling pressures seen with CPT. In conclusion, the central hemodynamic effects of CPT differ significantly from other vasodilator drugs used in the treatment of heart failure patients. These effects cannot be characterized simply in terms of "balanced" peripheral arterial and venous vasodilation; CPT exerts highly complex effects on peripheral vessels as well as having actions independent of its peripheral vasodilator effects.