Background Intractable epilep sy may be due to multidrug re sistance induced by conventional antiepileptic drugs1 The phenomenon is sometime s a ssociated with an overexpre ssion of multidrugre sistance gene 1(MDR1).The purpo se of this study wa s to determine if the overexpre ssionof MDR1 could be induced in a strocyte s from rat brains in vitro using antiepileptic drugs.Methods 　Astrocyte cell culture s from po stnatal Wistar rats (within 24 hours of birth)were e stablished.Different concentrations of the antiepileptic drugs phenytoin,phenobarbital,carbamazepine,and valproic acid were added to the culture s for 10,20,or 30 days.The expression of Pglycoprotein(Pgp),the protein product of MDR1,was inve stigated with immunocytochemistry.Results Less than 5 % of normal,untreated a strocytes had detectable Pgp staining at any time point.Phenytoin,phenobarbital,carbamazepine,and valproic acid induced the overexpre ssion of Pgp in a strocytes in a do se-and time2dependent manner.Significantly higher levels of Pgp staining were detected at therapeutic concentrations of certain antiepileptic drugs(20 μg/ ml phenobarbital,40 μg/ m.phenobarbital,and 20μg/ ml phenytoin)on day 301 Upregulation of Pgp was detected when using higher concentrations of phenytoin,phenobarbital,and valproic acid on day 20 and when using higher concentrations of any of the four antiepileptic drugs on day 30.Conclusions Treatment with antiepileptic drugs may contribute to the over expression in a strocytes of MDR1 and its protein product,Pgp.Themechanism leading to MDR must be considered in patients undergoing long-term treatment with antiepileptic drugs.