In this study we have investigated the prevalence and type of preC mutants in anti-HBe/HBV-DNA-positive patients with chronic hepatitis B in an endemic area. HBV-DNA from sera of 42 anti-HBe chronic HBV carriers was amplified by PCR and the preC region was directly sequenced. With one exception, all patients tested were found to be infected with viruses containing mutations in the preC region that predictably prevent precore and e antigen expression. Thirty-one patients were infected with HBV containing a stop codon; two had a mixture of wild-type and preC stop codon mutant; three had preC mutants with mutations in the translation initiation codon and two of them an additional stop codon; four had a frameshift mutation, and one had two stop codons. One patient was infected with a virus showing a mutation creating only an amino acid exchange which could not prevent HBeAg expression. The data obtained indicate a higher prevalence and heterogeneity of preC mutants in our geographical area than recognized so far in anti-HBe-positive carriers with chronic hepatitis B.