Prostaglandin E1 (PGE1, alprostadil) is a potent vasodilating agent that is frequently used to resolve cardiogenic pulmonary hypertension. To investigate the effect of PGE1 in refractory chronic heart failure in a double-blind trial, twenty patients (17 men, 3 women, 58 +/- 2 years, cardiac index < or = 2.5 l/min/m2, pulmonary capillary wedge pressure > or = 20 mmHg), who were in NYHA functional class IV on optimized treatment with ACE inhibitors and furosemide were infused with 30 ng/kg/min PGE1 or placebo through 48 hours. All patients received a concomitant therapy with standardized catecholamine infusions which were given 24 hours in advance and were continued throughout the study. There was no difference in baseline values between the randomized groups before PGE1 or placebo was added. PGE1 resulted in decrements in pulmonary artery pressure (from 37 +/- 4 to 30 +/- 4 mmHg; p < 0.01), pulmonary capillary wedge pressure (from 26 +/- 4 to 19 +/- 3 mmHg p < 0.001) systemic vascular resistance index (from 2048 +/- 213 to 1506 +/- 13 dyn.sec/cm5.m2, p < 0.05) and in increments in cardiac index and stroke volume index (from 2.2 +/- 0.1 to 2.8 +/- 0.2 l/min.m2; p < 0.05 and from 23 +/- 2 to 28 +/- 2 l/m2; p < 0.05, respectively). Moreover, creatinine clearance increased (p < 0.05). Placebo infusions did not result in any hemodynamic or renal effect. Between groups percentage hemodynamic changes differed with respect to pulmonary artery pressure (p < 0.01), cardiac index (p < 0.05), stroke volume index (p < 0.05) and pulmonary vascular resistance index (p < 0.05). It is concluded that intravenous infusions with PGE1 may add further substantial benefit to the hemodynamic state in refractory heart failure patients who are already stabilized on i.v. inotropic support with catecholamines.