This study evaluates the correlations between liver histology, cytolysis, cryoglobulinaemia, co-infection with hepatitis B virus, and immunosuppressive treatment in renal transplant patients with HCV infection. Forty-five of 378 kidney recipients (January 1973-September 1993) had anti-HCV antibodies (prevalence = 11.9%) detected by second generation ELISA (Abbott Pasteur). Viral RNA was detected in those patients by RT-PCR in serum and liver. HCV-positive patients underwent liver biopsy to assess their liver tissue lesions according to Knodell's score. Patients were also screened for Hbs, Hbc and Hbe antigens (ELISA, Abbott) and cryoglobulins (immunobinding, SEBIA). Of the 45 HCV+ patients, 38 (84.4%) had persistent viral replication in the serum and 29 of the 30 patients having undergone liver biopsy had PCR-positive liver tissue. The liver biopsies revealed no active hepatitis lesion in 14 patients (46.6%, Group CAH-), 16 (53.3%) had chronic active hepatitis (Group CAH+) and 3 (10%) had signs of cirrhosis. Comparing groups CH+ and CH- showed that viral replication was detected in all 16 patients with chronic active hepatitis, versus 10/14 patients in the CAH- group (P < 0.05). Patients were more frequently treated with azathioprine in the CH+ group (12/16 vs 8/14; P < 0.05). The duration of renal transplantation was significantly longer in patients with a Knodell score > 5 (58 +/- 56 months vs 35 +/- 29 months, P < 0.001). Incidence of co-infection with HBV was similar in both groups. The mean values of alanine aminotransferase correlated with the Knodell score (r = 0.4, P = 0.03). Mixed cryoglobulinaemia was more common in the replicant forms of HVC infection (12/38 vs 1/7, P < 0.0001). This study shows that liver histological lesions are correlated with HCV viral replication, are more frequent in patients treated with azathioprine and are more severe as the duration of transplant is longer.