The effects of intravenous infusion of the calcium antagonist, diltiazem (6, 30, and 150 mg/kg/hr) on cardiac and circulatory hemodynamics and on regional blood flow and cardiac output distribution to the major peripheral circulations were studied in conscious, normal Sprague-Dawley rats in the resting state. Therapy with diltiazem consistently increased cardiac output levels, as well as stroke volume, and decreased mean arterial pressure and systemic vascular resistance in a dose-related fashion. Diltiazem had a substantial effect on increasing coronary blood flow and reducing coronary vascular resistance. Effects of similar direction and magnitude were observed in the cerebral and hepatic arterial circulations. In a second study, rats were subjected to a submaximal treadmill exercise protocol during continuous intravenous infusion of either saline solution or diltiazem (DZ) in order to determine the effects of this agent on cardiac output distribution during exercise. The results indicate that the positive effects of diltiazem on cardiac output are maintained during exercise. The increase in cardiac output with diltiazem appears to be distributed throughout the major regional circulations in proportion to regional demand.