There are limited data on the use of lamivudine for patients with severe forms of acute hepatitis B. We report our experience with the use of lamivudine in six patients with acute HBV infection. Lamivudine was justified by disease severity for four patients and by concerns about risk of chronicity for two patients. The diagnoses of the treated patients were: fulminant liver failure (two patients), severe acute hepatitis B, protracted acute hepatitis B, and new HBV infection in the renal dialysis setting (two patients, one with severe liver injury). Serum HBV DNA titres ranged from 10(5) to 10(7) copies/mL prior to commencement of lamivudine. Lamivudine treatment was associated with a decline in serum HBV DNA and serum transaminases in all patients. All but one patient survived. A 58-year-old man with fulminant hepatitis and multiple organ failure died despite antiviral treatment. When possible, HBeAg and HBsAg seroconversion was documented during follow-up. In the absence of a randomized, prospective study of lamivudine in patients with severe acute hepatitis B, our data encourage the use of this safe and well tolerated drug.