Hepatic failure as a cause of death is increased in stable renal allograft recipients when compared with patients on dialysis. In order to assess the magnitude and the natural history of the hepatic functional derangement, the kinetics of xenobiotics which are metabolized by cytosolic (galactose) or microsomal (prednisolone, cyclosporine A) enzymes were determined in 28 consecutive stable kidney transplant patients 1 month and 1 year after transplantation. Renal transplant patients had a decreased mean (± S.D.) galactose elimination capacity at 1 month (6.26 ± 0.94 mg per min × kg) and at 1 year (5.93 ± 0.96 mg per min × kg), when compared with a different group of 28 healthy control subjects (7.52 ± 0.78 mg per min × kg, p < 0.001) and a decreased total body clearance of prednisolone at 1 month (2.13 ± 0.34 ml per min × kg vs. 2.71 ± 0.43 ml per min × kg in controls, p < 0.001), which further decreased over the following year to 1.76 ± 0.32 ml per min × kg (p < 0.001). The clearance of cyclosporine A declined significantly during the first year of successful transplantation (5.9 ± 2.1 ml per min × kg vs. 4.9 ± 1.2 ml per min × kg, p < 0.05). In conclusion, a substantial proportion of stable renal transplant recipients have decreased cytosolic and microsomal liver functions despite the absence of clinical and laboratory evidence of significant liver disease.