We studied the prevalence of hepatitis C virus (HCV) infection in 350 renal transplant (RT) patients with a functioning graft. The determination of HCV infection was based upon second-generation ELISA tests (ELISA-2, Abbott) confirmed by second-generation RIBA tests (RIBA-2, Chiron), including the proteins C22-3, C100-3, C33-C and 5-11. Three hundred and sixteen of these RT patients were on ciclosporin A (CsA) therapy with or without steroids (CS) and azathioprine (AZA); 34 received conventional immunosuppression. Eighty-seven RT patients were found to be HCV-positive (2.5%) when assessed by ELISA-2 tests; RIBA-2 was positive in 61 cases and 'indeterminate' in 26. Most of the HCV-positive patients had antibodies against C22-3 (94%), whereas antibodies against nonstructural antigens (C100-3, C33-C) were observed in 18 and 70% of cases, respectively. More than 88% of the HCV-positive patients were already HCV-positive before renal transplantation. Risk factors of developing HCV infection included: (i) the time on dialysis; (ii) the number of blood transufsions before transplantation, and (iii) the number of previous graft(s). There were significantly more HCV-positive patients among those on conventional immunosuppressive therapy (16 of 39) than among those on CsA (71 of 311; p < 0.02). Of those who where HCV-positive before transplantation, and for whom liver enzyme (LE) results were available (n = 68), 40 had either a normal or a transient increase in alanine aminotransferase (ALT) levels at that time, whereas 28 had a chronic increase in serum ALT +/- gamma-glutamyltranspeptidase levels. After transplantation, there was biochemical evidence of chronic liver disease in 33 patients (48.5%). Interestingly, 41 and 64% of those with respectively normal and increased LEs before transplantation presented with a biochemical chronic liver disease after RT. Surprisingly, 36% of those with a pretransplantation increase in ALT had normalized aminotransferase after transplantation. The daily doses of AZA, CS (i.e. prednisolone) were not statistically different between HCV-positive RT patients on conventional therapy (group A) and those on CsA (group B). Moreover, within each group, the daily doses of AZA, CS or CsA were not statistically different between those with a chronic increase in LEs and those with normal LEs. The percentage of HCV-positive RT patients with chronic abnormal LEs was not different between groups A and B. Surprisingly, the patients who were treated at least once for acute rejection with methylprednisolone pulses had a significantly lower incidence of chronic increases in LEs. Nine patients seroconverted for HCV after transplantation: 6 experienced a chronic increase in LEs. Finally, 7 of 87 patients were coinfected by HBV, all of them had a chronic increase in LEs. These results emphasize the fact that ALT alone cannot be used as a surrogate marker for chronic HCV infection in transplantation patients, thus a liver biopsy is required before and a few years after RT to assess liver damage in this population.