This study examined the effects of the dihydropyridine derivative nisoldipine (1.6 micrograms/kg/min) on hemodynamics and regional blood flow (radioactive microspheres, 15 +/- 5 microns) in conscious rats at rest and during treadmill exercises (35 feet/min, 5 min). Nisoldipine significantly reduced systemic vascular resistance (-38%) and mean arterial pressure (-17%) and increased heart rate (P less than .05). Skeletal muscle blood flow was increased and vascular resistances in the skeletal muscle, in renal and coronary arteries and in part of the gut circulations were significantly reduced (all P less than .05). Left ventricular end-diastolic pressure was unchanged by the drug both at rest and during exercise. At exercise, nisoldipine significantly increased skeletal muscle blood flow in four of eight skeletal muscle regions investigated; however, the increase in total skeletal muscle flow was less pronounced compared to the changes at rest. The vasodilator effect of nisoldipine in the renal and splanchnic circulations was markedly attenuated by the exercise-induced vasoconstriction in these circulatory beds. We conclude that nisoldipine is a potent vasodilator of skeletal muscle and coronary and renal arteries. It appears to possess highly selective effects on vascular smooth muscle as compared to its direct cardiac effects.