Using an oligonucleotide hybridization assay we studied the prevalence of wild-type and the predominant pre-core mutant hepatitis B virus in serum and liver of 49 antibody to hepatitis B e antigen carriers and three hepatitis B e antigen positive patients. Of the 45 serum samples from the anti-HBe carriers analyzed (no serum sample was available in four patients), 36 (80%) had hepatitis B virus DNA. In 26 of these 36 patients (72%) a mixed population was detected, wild-type genome alone was found in six patients (16%), the single mutant (nucleotide position 1896), in three cases (8%) and in one patient (2%) the viral DNA had the two nucleotide mutation (1896 and 1899). Of the liver biopsies from the 36 anti-HBe patients studied (no liver biopsy was available in 13 patients), 33 (92%) had hepatitis B virus DNA. A mixed viral population was detected in 23 patients (69%), only wild-type virus or a single mutation was found in eight (34%) and two patients (8%), respectively. In all cases, wild-type was the predominant genome. In serum and liver samples from the same patient, we found a concordance of the presence of wild-type HBV and the pre-core mutants studied in 23/26 (88%) of the patients. Alanine aminotransferase levels were higher (p<0.01) and the duration of hepatitis B surface antigen carrier lower (p<0.02) in patients with a predominance of precore mutant in comparison to wild-type. These data may indicate that in most cases, the presence of the HBV strains found in serum reflects the HBV genotypes which are infecting the hepatocytes. (C) Journal of Hepatology.