To evaluate the potential benefit of MDL 17043, a new inotrope-vasodilator agent, in the short- and long-term management of severe heart failure, its hemodynamic effects were determined after both intravenous (cumulative average dose 3.7 mg/kg) and oral (average 18.4 mg/kg) administration in 38 patients with severe intractable heart failure. After both intravenous and oral therapy, cardiac index increased from a control value of 2.1 ± 0.4 to 3.6 ± 0.9 liters/min per m 2, p<0.001 (intravenous) and from 2.2 ± 0.5 to 3.4 ± 0.6 liters/min per m2, p<0.001 (oral). Pulmonary capillary wedge pressure decreased from 26 ± 6 to 14 ± 7 mm Hg (p<0.001) and from 26 ± 7 to 18 ± 8 mm Hg (p<0.001) after intravenous and oral routes, respectively. Stroke volume index and stroke work index increased, and right atrial and pulmonary arterial pressures and systemic vascular resistance decreased by similar magnitude after both intravenous and oral MDL 17043 (all p<0.001). The hemodynamic effects persisted during 4 hours of observation. Thirty-seven patients were discharged while receiving MDL 17043 therapy and were followed up for a mean of 5.6 months (range 0.5 to 13). Thirty-three of the 37 patients had short-term improvement clinically by at least one New York Heart Association functional class. Undesirable effects, including nausea (35%), anorexia (27%), fluid retention (24%) and thrombocytopenia (<1%), necessitated discontinuation of therapy in 11 patients (30%) who were receiving multiple drug therapy. Six of seven patients who discontinued MDL 17043 on their own (out of the hospital) died within 1 week of doing so. In 24 patients who continued receiving longterm therapy, at a mean follow-up period of 6.1 months (range 1 to 13) there was a 50% mortality rate. Mortality was 62% for class IV and 18% for class III patients. Thus, if tolerated, MDL 17043 causes clinical improvement without apparently improving survival in patients with severe refractory congestive heart failure.