We describe lamivudine therapy for acute hepatitis B (AHB) with prolonged high alanine aminotransferase (ALT) and HBV DNA. Three male patients (27-31 years old) had prolonged high ALT, bilirubinemia, and prolonged prothrombin time for over 10 days. Lamivudine was administered at a dose of 150 mg per day because of the threat of acute liver failure. All three patients tolerated the drug well. Serum HBV DNA levels quickly became undetectable, and both the ALT level and liver function tests normalized within 1 month in all three patients. HBeAg and HBsAg disappeared during the clinical course of AHB, and HBsAb was not detected in two of the three patients during the 1-year follow-up. Direct sequence analysis revealed no significant substitution of amino acids in the precore and core regions, including the HLA class II epitope. Lamivudine might prevent the progression of severe AHB to fulminant liver failure, and it appears to modify the clinical course of the disease.