The purpose of this study was to examine effects of nimodipine (Bay e 9736), a calcium blocker, on constrictor responses of cerebral vessels in vivo. Pial artery diameter was measured in anesthetized cats. In the control state, sympathetic nerve stimulation, acute hypertension, and hypocapnia produced maximal decreases in pial artery diameter of 13.7 +/- 1.4, 12.1 +/- 2.7, and 13.3 +/- 2.7% (SE), respectively. Low doses of nimodipine (0.1-0.25 microgram X kg-1 X min-1) decreased the vasoconstrictor response to all three stimuli, and higher doses (0.5-1.0) virtually abolished the response (P less than 0.05 vs. control). In other experiments in cats and monkeys, cerebral blood flow (CBF) was measured with microspheres during acute increases in arterial pressure. Elevation of arterial pressure by approximately 40 mmHg in cats produced only a modest increase in CBF from 48 +/- 3 to 57 +/- 3 ml X min-1 X 100 g-1 in the control state and a larger increase in CBF from 53 +/- 6 to 87 +/- 9 ml X min-1 X 100 g-1 during nimodipine (P less than 0.05, control vs. nimodipine). Nimodipine also inhibited autoregulatory vasoconstriction in monkeys. Nimodipine, in the doses used, had only modest effects on resting vessel diameter, CBF, or arterial pressure. We conclude that nimodipine inhibits cerebral vasoconstrictor responses to several physiological stimuli in vivo.