We examined the effect of isradipine, a blocker of L-type voltage-sensitive Ca2+ channels (VSCCs), on the ischemia-induced release of dopamine in the rat striatum. Perfusion of 200 micrograms/ml isradipine in the striatum did not alter extracellular dopamine concentrations monitored by microdialysis. However, a marked increase (145-fold) in dopamine level during forebrain ischemia, developed by bilateral carotid artery occlusion, was attenuated significantly by 37% by isradipine whereas the intensity of ischemia, monitored by striatal blood flow, was unchanged. These results suggest that isradipine attenuates the ischemia-induced release of dopamine via blockade of L-type VSCCs on dopaminergic neurons.