purpose: Liver disease is a frequent complication in renal transplant recipients. To understand the nature and progression of hepatic disease in these patients, we performed percutaneous biopsies in 77 subjects who had chronic liver dysfunction in the posttransplant period. The purpose of the present investigation is to delineate the morphologic spectrum of chronic liver disease in the renal allograft recipients and to characterize the clinical and histologie progression of each of the different morphologic forms. patients and methods: Between 1971 and 1990, 915 patients received renal transplants at the Hennepin County Medical Center, Minneapolis, Minnesota. One hundred nineteen (13%) of them had abnormal liver function that persisted for longer than 6 months. Percutaneous liver biopsies were performed in 77 of these patients, but adequate tissue for histologie evaluation was available in only 72. After the biopsy, the clinical and histologie course of each subject was monitored in relation to the baseline hepatic morphology. To assess the predictive value of serum enzymes in diagnosing the histologie lesions, the level of serum enzymes at the time of the biopsy was correlated with the morphologic diagnosis. In addition, several clinical, biochemical, etiologie, and histologie variables were screened for their association with histologie progression to liver cirrhosis. results: The morphologic diagnosis in the 72 specimens evaluated at baseline was as follows: fat metamorphosis in 8 (11%), chronic persistent hepatitis in 20 (28%), early chronic active hepatitis in 20 (28%), advanced chronic active hepatitis in 15 (21%), and hemosiderosis in 9 (12%). There was no statistical correlation between the serum enzyme levels and the histologie diagnosis. During a mean follow-up of 5.7 ± 3.9 years, clinical progression to hepatic failure and death occurred in 35% of patients with early chronic active hepatitis, 55% with hemosiderosis, and 60% with advanced chronic active hepatitis. None of the patients with the morphologic diagnosis of fat metamorphosis or chronic persistent hepatitis died as a consequence of hepatic failure. Follow-up liver specimens were obtained in 34 (47%) of the original 72 subjects after a mean interval of 4.5 ± 4.3 years. Of the 15 patients with the initial diagnosis of early chronic active hepatitis, 9 (60%) showed morphologic transition to advanced chronic active hepatitis, and in 1 of the 5 patients with hemosiderosis (20%), the lesion had resolved after successive phlebotomies. During the follow-up, 60% with early chronic active hepatitis (9 of 14), 66% with hemosiderosis (2 of 3), and 100% with advanced chronic active hepatitis (4 of 4) showed histologie progression to liver cirrhosis. On the contrary, no morphologic alterations were observed in the follow-up specimens of patients with fat metamorphosis or chronic persistent hepatitis. Of the different variables screened for their association with histologie progression, older age at transplant, female sex, and morphologic diagnosis of advanced chronic active hepatitis were found to be significant. conclusion: Histologie diagnosis can be a useful marker in predicting the course of chronic liver disease after renal transplantation. Liver biopsy should be incorporated into the evaluation and management of chronic liver disease in renal transplant recipients.