Spiny neurons in the neostriatum are highly vulnerable to cerebral ischemia. Recent studies have shown that the postischemic cell death in the right striatum was reduced after ipsilateral dopamine denervation whereas no protection was observed in the left striatum after dopamine denervation in the left side. In order to reveal the mechanisms of such asymmetrical protection, electrophysiological changes of dopamine-denervated striatal neurons were compared after ischemia between the left and right striatum using intracellular recording and staining techniques in vivo. No difference in cortically evoked initial excitatory postsynaptic potentials was found between the left and right striatum in intact animals after ipsilateral dopamine denervation. The initial excitatory postsynaptic potentials in the dopamine-denervated right striatum were suppressed after transient forebrain ischemia while no significant changes were found in the dopamine-denervated left striatum. Paired-pulse tests suggested that these changes involved presynaptic mechanisms. Although the incidence of a late depolarizing postsynaptic potential elicited by cortical stimulation increased after ischemia in both sides, the increase was greater in the left side. The analysis of current-voltage relationship of spiny neurons indicated that inward rectification in the left striatum transiently disappeared shortly after ischemia whereas that in the right side remained unchanged. The intrinsic excitability of spiny neurons in both sides were suppressed after ischemia, however, the suppression in the right side was stronger than in the left side. The above results demonstrate that after ipsilateral dopamine denervation, the depression of excitatory synaptic transmission and neuronal excitability in the right striatum is more severe than that in the left striatum following ischemia. The depression of excitatory synaptic transmission and neuronal excitability, therefore, might play an important role in neural protection after ischemic insult.