We studied the effect of a prior unilateral substantia nigra lesion on the recovery of local cerebral glucose utilization (lCMRgl) and blood flow (lCBF), measured autoradiographically, following 30 minutes of forebrain ischemia in rats. On the lesioned side, striatal dopamine (DA) and its metabolites were depleted by more than 95% and did not change after ischemia. In contrast, significant increases in striatal DA metabolites occurred on the nonlesioned side following ischemia. Despite unilateral DA depletion, no side-to-side lCBF differences were observed. However, the normally occurring postischemic restoration of lCMRgl in the dorsolateral striatum at 2 and 4 hours of recirculation was suppressed on the DA-depleted side, and the degree of lCMRgl/lCBF uncoupling diminished. These results suggest that integrity of the DA system accentuates postischemic metabolism/flow uncoupling in the striatum and may therefore contribute to selective ischemic injury of this structure.