Improvement of graft survival after orthotopic liver transplantation is often attributed to cyclosporine. In order to assess the effects on liver function and histology, we compared the results of conventional immunosuppression (azathioprine/prednisolone = group I) and a triple drug regimen, which included CsA (group II) during the first year after transplantation. Group I consisted of 33 patients; group II of 18 patients. Significant differences are present in favor of the CsA regimen with regard to transaminases and cholestatic parameters. Liver synthesis function was slightly better, though already very good under conventional immunosuppression. One week after transplantation, normal histology was not observed in group I, while 90% of the patients showed acute rejection. In group II, 53% of the patients showed normal histology; only 40% of the patients in group II showed acute rejection (P<0.0002). One year after transplantation, liver histology was normal in 57% of the conventionally treated patients and in 90% of the CsA-treated patients. Also, less rejection occurred in group II during the first year after transplantation. Oneyear graft survival was 67% in group I and in group II 75%, which is not statistically different. Creatinine clearance did not differ in both groups. However compared with pretransplantation creatinine clearances, kidney function in the CsA-treated patients decreased with approximately 20 ml/min. These results show that liver synthesis and liver function are better under the CsA-containing triple-drug-maintenance regimen, which is supported by the far better liver histology. Kidney function is reduced, even under low dose CsA treatment.