Cyclosporin nephrotoxicity is a well-known complication in organ transplantation. In successful liver transplantation, a moderate degree of renal impairment is accepted. Whether this impairment is continuously progressive, stabilizes with time, or is reversible is not known. We have prospectively evaluated the glomerular filtration rate (GFR) using 51CrEDTA plasma clearance in 29 liver transplant patients (11 males and 18 females) with a mean age of 49 years (range 22-62 years). The 51CrEDTA plasma clearance measurements were performed preoperatively and at 3, 6, 12, 24, and 36 months after the liver transplantation. All but six patients were given sequential, quadruple drug therapy with antithymocyte globulin, azathioprine, steroids, and cyclosporin. Intravenous cyclosporin was avoided and oral cyclosporin started when renal function was stable. Cyclosporin was started in a dose of 8 mg/kg body weight, aiming at whole blood through levels (specific monoclonal technique) of 200 micrograms/l in the postoperative period; thereafter, the dosage was rapidly tapered down, aiming at whole blood trough levels of less than 100 micrograms/l at 3 months (1.5-2 mg/kg body weight). From a mean preoperative GFR of 89 +/- 3 ml/min per 1.73 m2, all patients declined in renal function after transplantation to a mean of 64 +/- 4 ml/min per 1.73 m2 3 months after transplantation, and starting in the 3rd month the renal function was stable at about 70% of the preoperative value. No correlations were found between cyclosporin peak level or accumulated cyclosporin dose and renal impairment. We conclude that liver transplantation with cyclosporin immunosuppression will induce renal impairment even if cyclosporin blood levels are carefully monitored and kept low.(ABSTRACT TRUNCATED AT 250 WORDS)