We studied the activity and stage of chronic liver disease in 45 HCV-seropositive/HIV-seronegative patients with severe haemophilia followed for at least 10 years. HCV-RNA was detected in serum in 36 patients (80%) Viraemic cases were further analysed for HCV genotypes: 10 (28%) were infected by type 1a, 10 (28%) by type 1b, seven (19%) by type 2, four (11%) by type 3, four (11%) had mixed infections (one by 1a + 1b, one by 1a + 2, one by type 2 + 3, and one by 1a + 2 + 3). ALT levels were within the normal range in 55% of the HCV-RNA negative patients but in only 11% of the viraemic cases. Results show a trend for higher levels of ALT in HCV-RNA-positive patients compared with those without viraemia (98 +/- 56 v 60 +/- 61), and particularly with patients with type 3 HCV infection (148 +/- 44). We suggest that a slow progression of chronic liver disease occurs in haemophilic HCV-positive/HIV-negative patients and conclude that presence of HCV-RNA in serum correlates well with cytolitic damage but, in the time-scale of our follow-up period, commonly used clinical-laboratory parameters cannot predict the chronic evolution of liver infection or identify differences in disease progression in relation to specific HCV subtypes.