Previous studies have shown that acute systemic administration of ethanol-induced striatal ascorbic acid (AA) release in mice and rats. In the present study, in vivo brain microdialysis coupled with high performance liquid chromatography (HPLC) with electrochemical detection (ECD) was used to comparatively evaluate the effects of clozapine on ethanol-induced AA release in mouse and rat striatum. The results showed that clozapine, at the dose of 15mg/kg i.p., had no effect on basal AA or ethanol-induced AA release in rat striatum. The potentiating effect of clozapine on ethanol-induced striatal AA release was still observed in rats, at the higher dose of 30mg/kg. In contrast, clozapine significantly inhibited ethanol-induced AA release in mouse striatum, at the dose of 15 and 30mg/kg, without affecting basal AA release. The present study suggested that clozapine differentially regulated ethanol-induced AA release in the mouse and rat striatum.