The prevalence of antibodies to hepatitis C virus (anti-HCV) was studied using a second-generation ELISA test in 121 patients with self-limiting acute hepatitis B, including 63 intravenous drug addicts (IVDA). Within the first month after the onset of illness, 47.1% of the patients were anti-HCV positive, this figure reaching 52.1% six months later. The prevalence in the sixth month was significantly higher in the IVDA (93.6%) than in the non-IVDA (6.9%) (p < 0.00001). Among the IVDA, anti-HCV was more frequent in those with (100%) than in those without hepatitis delta virus (HDV) coinfection (84.6%) (p = 0.004). Of the 63 anti-HCV positive patients, 36 (57.1%) continued to exhibit abnormal transaminase levels for more than six months, while this was not observed in anti-HCV negative patients. These results show a high prevalence of infection by hepatitis C virus (HCV) in IVDA with acute B hepatitis. As a rule, infection by HCV occurred prior to the hepatitis B infection, although occasionally simultaneous infections were observed. HCV appears to be the agent responsible for chronic liver disease in patients with acute B hepatitis who become HBsAg negative.