The effect of the bipyridine compound, amrinone, on tension generation in neonatal and adult myocardium was studied over the concentration range 30-500 Mg/ mL. Increasing concentrations of amrinone caused a monotonic increase in twitch tension and the rate of tension development in adult papillary muscles. In contrast, lower concentrations of amrinone (30 and 100 ng/ mL) caused a decrease in twitch tension and dP/ dt in newborn papillary muscles, whereas 500 µg/ mL amrinone caused a significant increase in both parameters in the younger age group. Lactic acid, used to dissolve amrinone, was shown to have no effect on tension development. Half relaxation time was decreased in adult preparations at all concentrations of amrinone. In comparison, the decrease in half relaxation time produced by amrinone in the newborn was significant only at a concentration of 500 jug/ mL. Action potential duration in the newborn was significantly shortened by 30 /ug/ mL amrinone. In voltage clamp experiments, 30 Mg/ mL amrinone was shown to have no effect on tension accompanying two second voltage clamp steps to the plateau potential in newborn myocardium. Developed tension at 400 ms into the clamp step, final tension, and the ratio of early peak tension to final tension were all unchanged by the low concentration of amrinone. In contrast, 500 µg/ mL amrinone in the newborn increased tension at 400 ms and final tension but had no effect on the ratio of early peak tension to final tension. These results suggest that the negative inotropic effect of lower concentrations of amrinone on neonatal myocardium is the result of changes in action potential configuration and not a true alteration in basic mechanisms of intracellular Ca2+regulation. Further, the positive inotropic effect of higher concentrations of amrinone appears to result from enhancement of transmembrane Ca2+influx as well as augmentation of Ca2+sequestration and rerelease by the sarcoplasmic reticulum.