Numerous cases of chronic hepatitis have been shown to be closely associated with persistent infection with hepatitis B virus (HBV). A group of 100 patients suffering from chronic active hepatitis (CAH) was investigated for HBV serologic markers. Of these, 35 patients were HbsAg-positive; in 26 HBsAg-negative subjects, anti-HBc were detected using counterimmune electrophoresis and complement-fixation tests. These data suggest that chronic liver disease in patients who were only anti-HBc-positive might be related to persistent infection with hepatitis B virus. Epidemiological clinical and histopathological data were different when we compared CAH patients who were HBsAg-negative, but anti-HBc-positive, with HBsAg-positive CAH patients. A sequence is proposed leading from HBsAg-positive to HBsAg-negative CAH, cirrhosis, and hepatoma in temperate areas, according to a model similar to the one described in intertropical Africa.