Background 　Intractable epilepsy may be due to multidrug resistance induced by conventional antiepileptic drugs.The phenomenon is sometimes associated with an overexpression of multidrug resistance gene 1(MDR1).The purpose of this study was to determine if the over expression of MDR1 could be induced in a strocytes from ratbrains in vitro using antiepileptic drugs. Methods 　Astrocyte cell cultures from po stnatal Wistar rats(within 24 hours of birth)were established1 Different concentrations of the antiepileptic drugs phenytoin,phenobarbital,carbamazepine,and valproicacid were added to the cultures for 10,20,or 30 days.The expre ssion of P-glycoprotein(Pgp),the protein product of MDR1,was investigated with immunocytochemistry1 Results 　Less than 5 % of normal,untreated a strocyte s had detectable Pgp staining at any time point.Phenytoin,phenobarbital,carbamazepine,and valproic acid induced the overexpre ssion of Pgp in a strocyte s in a do se- and time-dependent manner.Significantly higher levels of Pgp staining were detected at therapeutic concentrations of certain antiepileptic drugs( 20 μg/ ml phenobarbital,40 μg/ ml phenobarbital,and 20μg/ ml phenytoin)on day 30 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 overexpre ssion in a strocyte s of MDR1 and it s protein product,Pgp1 The mechanism leading to MDR must be considered in patient sundergoing long2term treatment with antiepileptic drugs.