The frequency and occurrence of HBsAg and HBcAg in 112 consecutive, HBsAg sero-positive, liver biopsies were determined using immunoperxidase staining, HBsAg and HBcAg were demonstrated in 35 (31.3%) and 71 (63.4%) biopsies, respectively. HBsAg in liver was found in the cytoplasm as diffuse granules, mostly in the form of cytoplasmic inclusions. There was also perinuclear and membranous patterns. HBcAg in liver was found mostly in the cytoplasm and occasionally confined to the nucleus. The highest correspondence between HBsAg positivity in serum and liver was found in cases with normal histology morphology (80%). The frequency of HBs and HBcAg in liver in chronic liver disease was 23.1~50% and 36.4~69.2%. According to the variable expression pattern of HBs & c Ags in liver cells, 47 cases (42%) showed only HBcAg in liver. Twenty-nine cases (25.6%) failed to demonstrate any HBV Ags in liver and 24 cases showed boty antigens in liver. No correlation was found between liver disease groups and HBV Ag expression patterns. However, 11 cases (9.8%) showed only HBsAg in liver; predominant HBsAg pattern was observed in 80% of "normal histology group". 73.2% of HBsAg positive patients had anti-HBc in serum and 57.7% of them had HBeAg. 70.3% of anti-HBc positive and 70.7% of HBeAg sero-positive patients had HBcAg in liver cells. These findings strongly suggest that the presence of HBcAg. Serum HBeAg and anti-HBc can be used as a reliable indicator of active viral replication. The overall results further suggest an interplay of both hepatitis B virus and host immune response in the development and pathogenesis of hepatitis, including different degrees of accumulation of HBsAg and HBcAg in the liver and the various histological types of hepatitis.