The hemodynamic effects of milrinone (Mil) were studied in 11 patients with congestive heart failure (CHF) and New York Heart Association (NYHA) functional class II-IV before and after a 2-week treatment. The plasma concentration of Mil was also determined and its pharmacokinetics analyzed. The effect of a placebo was examined before the initiation of the treatment. At the onset, the hemodynamic effects of a single oral dose of Mil (7.5 mg) were evaluated. Mil increased the cardiac index significantly (p<0.05) 4 h after administrations from 2.3 +/- 0.4 to 2.9 +/- 0.6 L/min/m2 . The pulmonary capillary wedge pressure (PCW) was lowered significantly by Mil (p<0.05) between 0.5 and 4 h after administration. After a 2-week treatment, the baseline PCW dropped (p<0.05) and the NYHA functional class improved in 10 patients. One patient remained in the same class (II). The improved NYHA class was maintained in 6 patients tested after a mean interval of 16 +/- 3 months. Single oral administration of Mil (7.5 mg) induced hemodynamic improvements after 2-week treatment and the drug also induced similar improvements even after the chronic oral therapy with Mil for 16 +/- 3 months. Pharmacokinetic analysis showed a significant increase in the area under the curve after 2 weeks of treatment. We conclude that Mil decreases the PCW and probably increases the cardiac index and thus improves the symptoms and NYHA functional class in patients with CHF.