Amrinone (50-1,000 microgram/ml) produces a dose-dependent inotropic action on rabbit papillary muscle. The hypodynamic state following prolonged stimulation is prevented or abolished by amrinone, and contractile force remains significantly elevated over drug-free controls throughout the ensuing 3-h duration of exposure. In a concentration of 1 mg/ml, dysrhythmic phenomena occasionally appeared, e.g., bigeminy, automaticity, and elevated threshold to electrical stimulation. Bigeminy could be abolished either by increasing the external K+ concentration in the bathing media, or by raising the stimulating voltage. However, amrinone failed to alter the refractory period following 60 min of exposure. In isolated perfused guinea pig Langendorff heart preparations, amrinone (50 microgram/ml) significantly increased coronary flow, myocardial oxygen consumption (MVO2), cardiac work, and, during the period of peak activity, dP/dt. However, it had no significant effect on cardiac efficiency. And, as in the papillary muscle preparation, the effect of amrinone was easily reversed by perfusing the preparation with fresh (no-drug) media. Preliminary evidence shows that amrinone fails to reverse the negative inotropic action of verapamil as well as calcium-free media, although the effects on heart rate, coronary flow, and MVO2 were reversed. However, the higher the external calcium concentration, the greater was the level of contractile response achieved by amrinone. Thus, the mechanism of amrinone-induced augmentation appears to be dependent upon the availability of calcium.