The biochemical and virological outcomes of 19 patients with chronic hepatitis B who had been treated with 100 mg per day of lamivudine (LMV) for 1 year from 1995 to 1996 were evaluated. Fourteen patients were followed for 4.5-5 years since the end of the treatment without any further active antiviral treatment. During the treatment, DNA levels of hepatitis B virus (HBV) were under the detection limit of a hybridization assay in all the 19 patients. However, YMDD mutants appeared in 5 (26%) patients during the course of treatment and were accompanied in all five by the elevation of serum alanine aminotransferase (ALT). Mutated HBV DNA was not detected at 1 year after the end of treatment in any of the 5 patients. Of the patients who were followed for 4.5-5 years, the rate of seroconversion to anti-HBe and negativity for HBV DNA fluctuated during the course. Four of 11 patients who initially had been positive for hepatitis B virus e antigen (HBeAg) became positive for anti-HBe and all of them remained positive for HBV DNA by a transcription-mediated amplification test at the end of the follow-up. Thus, a 1-year treatment with LMV for chronic hepatitis B resulted in the relapse of HBV viraemia in most of the patients who had been positive for HBeAg, although the clinical course ameliorated in some patients. In addition, HBV DNA remained positive and ALT values were elevated at the end of the follow-up in the three patients who had been treated with interferon, with or without LMV, during the follow-up.