The multi-drug resistance protein -1 or P-glycoprotein-1 ( P-gp1) functions as Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells. Increased P-gp1 expression in lymphocytes of patients with systemic lupus erythematosus (SLE) may influence steroid requirements for disease control. This study evaluates P-gp1 functional activity in CD5+, CD7+ and CD20+ lymphocytes in SLE children and its impact on clinical outcome. 44 SLE children and 50 healthy controls were studied. Estimation of P-gp1 function was based on the efflux of Rhodamine-123 using flow cytometry. Results were expressed as percentage of lymphocytes with high P-gp1 activity. The P-gp1 function in CD5+, CD7+ and CD20+ lymphocytes was significantly higher in patients compared to controls (with P value < 0.05 for each lymphocyte population). The expression of active P-gp1 in CD5+ and CD7+ lymphocytes correlated positively with disease activity as estimated by SLEDAI and ESR. P-gp1 expression in SLE lymphocytes was also found to correlate significantly with some disease manifestations specially lupus nephritis, thrombocytopenia and ANA positivity. Steroids low responders whose SLEDAI were > or = 11 while receiving 1 mg/Kg/day of prednisolone demonstrated higher P-gp1 functions in CD 5+ and CD 7+ lymphocytes compared to high responders whose SLEDAI were < 11 while receiving < 1 mg/Kg/day of prednisolone. CD5+ lymphocyte's P-gp1 function was found to be lower in the patients receiving cyclophosphamide in addition to steroids compared to those on steroids only. It is concluded that measuring P-gp1 function in CD5+ and CD7+ lymphocytes could be one of the prognostic and therapeutic indices in SLE.