HBV chronic infection is an important health problem. The HBV core antigen carries several epitopes for T and B cell recognition and the immune response is crucial for determining the outcome of viral infection. Using PCR-RFLP several point mutations were detected in the HBV core ORF of HBV extracted from the serum of 140 chronically infected patients and 86 samples from another 37 patients followed-up in a longitudinal study. Mutations at position 2248 and 2147 (A3) and at 2038 (M2) were found most frequently. The wild type core genotype was found in about 50% of the samples. PCR-RFLP results were confirmed by direct sequencing of amplified products from HBV DNA present in chronically infected patients. The method is rapid and reliable and may be particularly useful for a rapid detection of viral mutants in a large number of patients.