A 32-year-old man of Finnish origin was admitted to the University of Helsinki hospital for renal transplantation. Chronic glomerulonephritis was diagnosed 2.5 years before admission; consequent severe hypertension and edema were treated with atenolol, minoxidil, and furosemide with a relatively poor response. During that time, the patient also had an episode of bacterial pleuritis that was treated with antibiotics and finally by decortication of the right lung. Regular hemodialysis treatment, initiated 1.5 months before admission, resulted in weight loss from 113 kg to 79 kg. The patient was transfused six times with leukocyte-poor blood from random donors. On admission, his urine output was 500 mllday. The patient underwent uneventful renal transplantation receiving a DR-identical 3/0 mismatched kidney. The cold ischemia time was 41.5 hours. He was enrolled in a clinical trial comparing the efficacy of a regimen consisting of azathioprine and steroids versus cyclosporine and was randomized for treatment with cyclosporine alone. Cyclosporine was initiated at a dose of 10 mg/kg/day and was tapered to 6 mg/kg/day by day 18. The patient also received cimetidine, metoprolol, prazosin, furosemide, and digoxin. The patient's initial postoperative course was complicated by acute tubular necrosis, presumed secondary to the long preservation time. Urine output remained less than 100 mllday during the first week and increased to greater than 400 mI/day only on day 10 (Fig. I). The patient was hemodialyzed on alternate days during the first 2 weeks. He remained afebrile. Blood leukocyte and thrombocyte levels ranged between 6.6 and 8.1 x 109/liter, and 145 and 201 x 109/liter, respectively. Slight eosinophilia was recorded on day 5. The status of the allograft was monitored with fine-needle aspiration biopsies every other day beginning on the fifth day after transplantation. The first biopsy demonstrated slight lymphocytic and monocytic inflammation in the graft with severe parenchymal cell changes characterized by swelling and puffy vacuolization. Early lymphocytic-monocytic inflammation, without the presence of activated lymphoid cell forms, is characteristic of immunosuppression with cyclosporine alone, whereas the swelling and puffy vacuolization of the parenchymal cells represent the cytologic picture of acute tubular necrosis. On day 7, an elevation of lymphoid cells was noted in the graft, and lymphoid blast cells appeared in the inflammatory population. This increase in inflammation, recorded on 2 consecutive days, corresponds to the cytologic picture of acute cellular rejection. Accordingly, the patient was treated with 2 to 3 mg/kg/day of steroids by mouth for 7 days. During this period, the inflammation subsided: blast cells disappeared from the aspirates and inflammatory mononuclear cells nearly disappeared. Concomitantly, the parenchymal cell morphology gradually improved. These findings were considered consistent with successful treatment of acute cellular rejection and with resolution of acute tubular necrosis. The steroid dose was reduced to 0.8 mg/kg/day and then gradually to 0.2 mg/kg/day; a small maintenance dose was continued. Concomitantly, the graft function improved significantly, the serum creatinine level fell, and dialysis was discontinued on day 12. On day 25, serum creatinine again increased. Fine-needle aspiration biopsy demonstrated lymphocytic and monocytic inflammation with no blast cells in the inflammatory infiltrate, On the other hand, the graft tubular cells, and to a lesser extent vascular endothelial cells, demonstrated clear isometric vacuolization. In immunoperoxidase staining, the graft tubular cells contained cyclosporine (or its immunologically cross-reactive derivatives). These findings were interpreted as representing cyclosporine nephrotoxicity. The cyclosporine dose was reduced from 6mg/kg/day to 2—3 mg/kg/day for 3 days and then was raised to 5 mg/kg/day. The serum creatinine level fell again, reaching a nearly normal level in the fifth postoperative week, The tubular cells returned to normal in the aspiration cytology. The patient was discharged in the fifth postoperative week. Since then, the serum creatinine has remained at 1.7—2.8 mg/dl (150 to 250 .tmol/liter). The remainder of his course was uneventful.