Neurons in the dorsal neostriatum are highly vulnerable to transient cerebral ischemia. It has been suggested that excessive dopamine release during ischemia may play an important role in the pathogenesis of postischemic cell death in the neostriatum. However, it remains controversial whether depletion of dopamine protects neurons in the neostriatum against ischemic insult. In the present study, transient forebrain ischemia was induced using the four-vessel occlusion method. Ischemic depolarization was used as an indication of completed ischemia. Under our experimental conditions, ischemia that produces approximately 21 min ischemic depolarization caused more than 90% of cell death in the dorsolateral neostriatum. Using such ischemia as a standard insult, the effect of dopamine depletion on neostriatal neurons after ischemia was investigated. Dopamine depletion was produced by unilateral injection of 6-OHDA into the substantia nigra. No difference was found between the number of surviving neurons in the left and the right neostriatum after depletion of dopamine on the left side. In contrast, surviving neurons dramatically increased in the right neostriatum after depletion of dopamine on the right side. These results clearly demonstrate an asymmetrical protection of neostriatal neurons against ischemia after dopamine depletion. The mechanisms of this asymmetrical protection may clarify dopamine action on neuronal injury following cerebral ischemia.