The effect of cyclosporine doses on renal P-glycoprotein expression was examined. Rats were given cyclosporine orally at 2, 10, 30 mg/kg/day or subcutaneously at 1, 5, 15 mg/kg/day for 28 days with or without 14 days of additional vehicle dosing. Following cyclosporine dosing, renal function and P-glycoprotein expression were measured. Renal function was reduced in rats receiving oral cyclosporine and the highest subcutaneous dose, 15 mg/kg/day. Western blot analysis showed that cyclosporine administered orally at 10 and 30 mg/kg/day and subcutaneously at 15 mg/kg/day induced significantly renal P-glycoprotein expression. After discontinuation of cyclosporine, renal P-glycoprotein returned to pre-dosing levels in oral groups, whereas the return was incomplete in subcutaneous groups. These results indicate that cyclosporine induces renal P-glycoprotein overexpression a dose-dependent manner.