The efficacy of nimodipine in preventing ischemic brain injury was tested in rats subjected to a 20-minute period of high-grade forebrain ischemia by 4-vessel occlusion. Three minutes after restoration of circulation to the brain, an intravenous bolus of 5 micrograms/kg nimodipine or an equivalent amount of vehicle or saline was given, followed by continuous intravenous infusion of the respective solution at 1 microgram/kg/min for 2 hours. In a second series, a larger bolus (20 micrograms/kg of nimodipine) and longer infusion period (6 hours) were employed. Histopathology of the brain was evaluated blindly 72 hours later and graded on a conventional 3-point scale. There was no significant effect of treatment in either series. In the 6-hour series, the percent of cerebral hemispheres showing damage of Grades 2 or 3 in zone CA1 of the hippocampus and in the striatum, respectively, was 100 and 40% for the nimodipine-treated rats, 100 and 42% for rats receiving vehicle, and 75 and 25% for animals receiving saline. Thus, this study revealed no beneficial effect of nimodipine when given following a 20-minute period of severe forebrain ischemia.