A whole blood lymphocyte proliferation assay was compared to a standard method requiring the isolation of lymphocytes from blood. Both methods were used to measure inhibition of proliferative responses of phytohaemagglutinin (PHA1)-stimulated human peripheral blood lymphocytes by tacrolimus (FK 506(1)), cyclosporine A (CsA1), rapamycin (RA1), dexamethasone (DEX1), prednisolone (PR1), and methylprednisolone (MP1). Three of the drugs studied (FK 506, CsA, and DEX) yielded similar IC50 values with both methods. The whole blood proliferation assay produced modestly lower IC50 values for RA, PR and MP. The whole blood lymphocyte proliferation method is simple and can be used when only limited volumes of blood can be obtained or isolation of cells gives unsatisfactory yields.