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We longitudinally evaluated the virological behaviour and the hepatitis B virus (HBV) genomic variability in inactive HBV surface antigen (HBsAg) chronic carriers.Fourteen HBsAg-positive healthy workers (13 inactive carriers and 1 with active HBV infection) were followed up for 12 months by monthly evaluation of aminotransferase, HBV DNA, and IgM anti HBV core antigen (IgM anti-HBc) values. Moreover, HBV serum isolates from each case were amplified, cloned and sequenced to evaluate the presence of the potentially clinical relevant core-promoter and precore mutations. The same technical procedures were used to examine the S gene of isolates from 3 randomly selected inactive carriers and the patients with active HBV infections.Aminotransferase values were constantly normal in all cases. Viremia levels appear to fluctuate widely over time in each individual case, although the HBV DNA remained below 2 × 104 copies/ml in all samples. Only four serum samples from two inactive carriers had IgM anti-HBc values higher than the specific cut-off limit of the assay. Either wild type or core-promoter/precore HBV variants or a mixture of them were detected in the inactive carriers. S gene nucleotide homology among the clones from the three inactive carriers and the subject with active infection was 98.9%, 98.3%, 98.1% and 98.2%, respectively.The degree of suppression of HBV replication in inactive carriers is variable over time, and the entity and quality of HBV variability is comparable between active and inactive carriers.