The effects of nilvadipine, a Ca2+ entry blocker, on focal cerebral ischemia were investigated in rats having unilateral middle cerebral artery occlusion. All rats had 24 h ischemia, and were divided into three groups (ten rats per group). Groups 1 and 2 received 1.0 and 3.2 mg/kg nilvadipine s.c. respectively, just after the occlusion. Control rats received an equal volume of the vehicle. Control animals had a % infarct volume of 28.2 +/- 11.4%, and a left/right hemispheric volume ratio of 112 +/- 12%. Group-1 and -2 rats had % infarct volumes of 25.5 +/- 11.6% and 13.9 +/- 9.2% (p less than 0.01) respectively, and left/right hemispheric volume ratios of 111 +/- 9% and 103 +/- 7% (p less than 0.05), respectively. Thus, the drug reduced the infarct size and the brain edema in a dose-dependent manner. The significant decrease in the infarct volume was observed in the periphery of the frontoparietal cortex. This study supports the hypothesis that nilvadipine may be a potential therapeutic agent for cerebral ischemia. Neuropathological findings suggest the possible therapeutic effects of the drug in the ischemic penumbra.