We studied hepatitis C virus (HCV) clearance and antibody reactivity patterns in a cohort of 100 haemophiliacs exposed to unsterilized blood products, of whom 25 were antiHCV negative and 75 were antiHCV positive [49 human immunodeficiency virus (HIV) negative and 26 HIV positive]. HCV RNA was measured by the 2.0 bDNA assay and an 'in-house' polymerase chain reaction assay. Antibody reactivity patterns were examined using a recombinant immunoblot assay (RIBA). Prior HCV infection was found in two (8%) of 25 antiHCV negative patients. HCV viraemia persisted in all 26 antiHCV+ patients who were coinfected with HIV. HCV RNA clearance was found in 12 (25%) of 49 antiHCV+, HIV- patients. Viral clearance was associated with younger current age (P < 0.01) and age at infection (P < 0.001), but not with duration of infection or with dose or frequency of clotting factor use. RIBA ratios reflecting an index of each patient's overall reactivity to four HCV epitopes were significantly lower in those with viral clearance (P < 0.0001). Over a period of 15 years, those with viral clearance demonstrated significant loss of reactivity to the NS3, NS4 and NS5 epitopes, while those with viral persistence demonstrated relatively stable reactivities to all epitopes. We conclude that spontaneous HCV RNA clearance in haemophiliacs is age-related and is unlikely to occur in those coinfected with HIV. The loss of antibody reactivity for some epitopes, especially c22 (core), may be a marker for the natural resolution of chronic HCV infection.