Six patients with severe congestive heart failure refractory to conventional therapy, including vasodilators, were treated with oral amrinone for a mean duration of 41 weeks (range 20 to 72 weeks). At initiation of therapy, the cardiac index increased from 1.74 +/- 0.31 to 2.62 +/- 0.52 (mean +/- SD) liters/min/m2 (p less than 0.01) and pulmonary capillary wedge pressure decreased from 26.5 +/- 3.5 to 19.5 +/- 5.4 mm Hg (p less than 0.05). Symptoms were alleviated and exercise capacity increased from 5.9 +/- 2.9 to 11.5 +/- 4.5 minutes (p less than 0.05). During long-term therapy, exercise capacity remained constants in three patients whereas it decreased in three others. All patients demonstrated an increase in heart size. Withdrawal of amrinone therapy precipitated severe symptoms at rest and hemodynamic deterioration in all patients. The cardiac index decreased from 1.87 +/- 0.49 to 1.32 +/- 0.30 liter/min/m2 (p less than 0.05) and pulmonary capillary wedge pressure rose from 20.6 +/- 2.9 to 28.8 +/- 5.6 mm Hg (p less than 0.05). These changes were reversed by reinstitution of therapy. Thus, amrinone-dependent hemodynamic benefits were demonstrated during long-term therapy without tachyphylaxis. In addition, progression of the underlying cardiac disease was observed in every patient.