&NA;The alterations in metabolism and cerebral blood flow that occur following transient focal ischemia were studied in rabbits anesthetized with halothane and subjected to transient occlusion of an M2 segment of the middle cerebral artery (MCA). The parameters measured included intracellular brain pH and focal cortical blood flow (fCBF)—assessed by the umbelliferone technique—electrocorticograms, and cortical microcirculatory changes. A gradient of ischemia developed in the cortex between the patent and occluded vessels. Cortical sites with moderate and severely diminished flow were examined as a function of time before and after occlusion. Mean preocclusion fCBF was 50.8 ± 2.1 ml/100 g/min, and brain pH was 6.99 ± 0.04. Following occlusion, fCBF fell to 14.6 ± 2.3 ml/100 g/min, with an intracellular pH of 6.53 ± 0.03 in sites of severe ischemia in the territory of the occluded vessel. Sites between the patent and occluded branches revealed moderate changes in fCBF and intracellular pH of 26.7 ± 3.6 ml/100 g/min and 6.74 ± 0.03 ml/100 g/min, respectively. Sites adjacent to the patent M2 branch remained similar to baseline. Pretreatment intravenously with nimodipine, a dihydropyridine class of Ca2+channel antagonist, improved flow in the territory of the occluded segment of the middle cerebral artery to 30.6 ± 2.2 ml/100 g/min, while maintaining the brain pH at 6.83 ± 0.03. Similarly, at sites intermediate between the patent and occluded M2 segments of the MCA, cortical blood flow remained at 53.5 ± 4.0 ml/100 g/min, and the pH at 6.95 ± 0.04, in 10 animals pretreated with nimodopine. This effect was apparently achieved by blocking the secondary, ischemia‐induced vasoconstriction known to occur in areas of focal incomplete ischemia.The diphenylalkylamine class Ca2+channel blockers was examined using verapamil. This was found to be without significant effect. The vehicle carrying nimodopine was also without effect. To authenticate further the reliability of MCA occlusion, a separate group of animals was examined with cautery occlusion of the M2 segment of the MCA. Nimodopine had an effect in this group of animals identical to that caused by occlusion of the vessel with a clip. Visual inspection of the cortex in control and treated animals revealed a marked difference in the development of cortical pallor and microcirculatory changes. We conclude that nimodopine protects the conducting vessels against the secondary vasoconstriction known to occur in areas of focal incomplete ischemia, and thus increases collateral flow. This agent may have the potential for brain protection in areas of incomplete focal ischemia from occlusion of a single major vessel. (Neurosurgery24:80‐87,1989)