P-glycoprotein (Pgp) is an ATP-dependent drug efflux pump responsible for classical multi-drug resistance (MDR). 2. Pgp is part of a supergene family of membrane transport proteins that includes the cystic fibrosis gene product. 3. Transfection of cells with the MDR1 gene has been previously shown to generate volume-regulated chloride channel activity in association with Pgp expression. 4. We have used whole-cell patch clamping to examine the drug-sensitive T lymphoblastic cell line CEM-CCRF and its classical MDR derivative CEM/VLB100. The results suggest that expression of Pgp is not associated with increased chloride channel activity in this multi-drug resistant cell line. 5. We were unable to confirm previously reported results in MDR1 transfected cell lines that suggested that Pgp was associated with the presence of volume-regulated chloride channels.