ABSTRACT— The incidence of HBV-DNA polymerase, HBV-DNA and serum and liver HBcAg in 104 chronic HBsAg carriers was studied. HBV-DNA was the most frequently detected marker, followed by HBcAg and HBV-DNAp. According to their individual or combined presence, four different serological patterns of viral replication were discerned: 53 patients had all these markers, 30 had HBV-DNA but lacked HBV-DNAp (15 with and 15 without HBcAg) and 21 had no such markers detectable. The simultaneous positivity for all of those markers was observed only in HBeAg-positive patients. HBV-DNA alone or along with HBcAg was found in a similar incidence irrespective of the HBe system. Liver HBcAg was found in all but four patients with and in four without HBV-DNA. Viral DNA concentration was significantly (p < 0.001) higher when HBV-DNAp tested positive. Indeed, HBeAg rather than anti-HBe patients had higher (p < 0.005) levels of HBV-DNA. In HBeAg-positive patients, the nuclear HBcAg staining was significantly (p < 0.05) higher when HBV-DNAp tested positive. In DNA polymerase-negative patients, but positive for HBV-DNA, those with or without HBcAg had a similar percentage of core antigen staining. The same distribution was seen in anti-HBe, HBV-DNA-positive patients. However, the mean percentage of hepatocytes displaying cytoplasmic HBcAg did not differ significantly among patients with HBV-DNA, irrespective of the HBe system and the HBV-DNAp status. Such patients had significantly (p < 0.001) higher ALT levels than those without viral DNA. Active viral replication can be assessed differentially through any of these serum markers and is associated with liver cell necrosis.