We performed in total 528 kidney transplantations from Feb. 1983 to Dec. 1988 in Kidney Center of Tokyo Women's Medical College. Of the 528 kidney transplantations, 450 were living related kidney transplantations. The living related renal transplant recipients treated with CYA were divided into 3 groups: high dose CYA double drug therapy group (group 1), high dose CYA triple drug therapy group (group 2) and low dose CYA triple drug therapy group (group 3). Group 1 (n = 263) was treated with CYA (initial dose 12 mg/kg) and methylprednisolone (MP). Group 2 (n = 106) was treated with CYA (initial dose 10 mg/kg), MP and azathioprine (AZ) (1 mg/kg). Immunosuppression of group 3 (n = 81) consisted of CYA (initial dose 6 mg/kg), MP and AZ (2 mg/kg) (or mizoribine (MZ) (3-5 mg/kg). CYA serum trough level (polyclonal) was lowered according to the initial dose of CYA, and in particular trough level in group 3 was controlled at a low level (50-150 ng/ml in induction phase) to reduce CYA nephrotoxicity. However, even if strict control of serum trough level was accomplished, we could not get improvement of renal function in Group 3. Group 3 had more frequent and severe accelerated acute rejections (AAR) than the other groups. These data showed that inadequate immunosuppression in group 3 caused more frequent and severe rejection episodes. Also, renal biopsy revealed CYA nephrotoxicity even in group 3 and this nephrotoxicity may have been caused by ischemic damage by severe rejections.(ABSTRACT TRUNCATED AT 250 WORDS)