Peripheral vascular and direct cardiac effects of calcium chloride were determined in a new animal model, the unanesthetized calf, before and after replacement of its natural heart (NH) with a pneumatically driven artificial heart (AH). Calcium (5 and 10 mg/kg) significantly increased cardiac output (Q1) and reduced systemic vascular resistance (SVR) before and after AH implantation. Increases in Q1in AH calves and reductions in SVR in both NH and AH calves were, however, transient, being present 5 minutes but not 15 minutes after both doses of calcium. Increases in Q1and reductions in SVR were significantly (P<.05) greater after 10 mg/kg than after 5 mg/kg calcium in NH and AH calves. Both doses of calcium produced greater (P<.05) increases of Q1in NH than in AH animals but similar reductions in SVR. Pulmonary vascular resistance, heart rate and pulmonary arterial and right atrial pressures were not significantly altered by either dose of calcium in NH or AH calves. Mean aortic pressure was influenced by 10 mg/kg calcium only, being transiently reduced in AH calves and increased in NH animals. Pulmonary shunt (Qs/Qt) was increased by both doses of calcium in NH calves but only by 10 mg/kg in AH animals. Correlations of mean change in Qs/Qtwith mean change in Qtwere high both before (r = .99) and after (r = .97) AH implantation. These data demonstrate that calcium significantly reduces SVR in a dose-related manner as well as exerting a positive inotropic effect on the myocardium.