The electrophysiologic effects of milrinone, a new inotropic agent, have not been characterized in humans. Accordingly, 10 patients with class III or IV congestive heart failure underwent hemodynamic and electrophysiologic testing before and during an infusion of milrinone (0.5 micrograms/kg/min). Cardiac index increased from a mean of 1.65 +/- 0.51 to 2.19 +/- 0.68 liters/min/m2 (p less than 0.03) and pulmonary artery capillary pressure decreased from 30 +/- 9 to 22 +/- 9 mm Hg (p less than 0.01), without a significant change in systemic arterial pressure. Holter monitoring was performed for 48 hours at baseline and during infusion of milrinone. Frequency of ventricular premature complexes and ventricular couplets did not change significantly. Frequency of ventricular tachycardia (VT) increased significantly, although no patients would be classified as having a proarrhythmic effect based on a clinical model. PR, QRS, QTc, heart rate, AH, HV, atrial, atrioventricular and ventricular effective and functional refractory periods were not affected. Milrinone decreased 1:1 atrioventricular maximal conduction from 399 +/- 133 to 374 +/- 111 ms (p less than 0.01); ventriculoatrial conduction was not significantly affected. During programmed right ventricular stimulation, 5 patients had inducible VT at baseline (3 sustained, 2 non-sustained), whereas after drug administration, none had it (p less than 0.05). Thus, intravenous milrinone is an effective inotropic drug that also enhances atrioventricular conduction and may decrease the incidence of inducible VT in patients with congestive heart failure.