Berberine, an alkaloid of the protoberberine family, has been shown to have strong positive inotropic and peripheral resistance-lowering effects in dogs with and without heart failure. To determine the acute cardiovascular effects of berberine in humans, 12 patients with refractory congestive heart failure were studied before and during berberine intravenous infusion at rates of 0.02 and 0.2 mg/kg per min for 30 minutes. The lower infusion dose produced no significant circulatory changes, apart from a reduction in heart rate (14%). The 0.2 mg/kg per min dose elicited several significant changes: (a) Decreases in systemic (48%, p less than 0.01) and pulmonary vascular resistance (41%, p less than 0.01), and in right atrium (28%, p less than 0.05) and left ventricular end-diastolic pressures (32%, p less than 0.01). (b) Increases in cardiac index (45%, p less than 0.01), stroke index (45%, p less than 0.01), and LV ejection fraction measured by contrast angiography (56%, p less than 0.01). (c) Increases in hemodynamic and echocardiographic indices of LV performance: peak measured velocity of shortening (45%, p less than 0.01), peak shortening velocity at zero load (41%, p less than 0.01), rate of development of pressure at developed isovolumic pressure of 40 mmHg (20%, p less than 0.01), percent fractional shortening (50%, p less than 0.01), and the mean velocity of circumferential fiber shortening (54%, p less than 0.01). (d) Decrease of arteriovenous oxygen difference (28%, p less than 0.05) with no changes in total body oxygen uptake, arterial oxygen tension, or hemoglobin dissociation properties.(ABSTRACT TRUNCATED AT 250 WORDS)