AIM: To study the efficacy of tenofovir disoproxil fumarate (TDF) at low dose in a small open trial of chronic hepatitis B patients with advanced stage disease.METHODS: Eleven patients were treated with TDF 75 mg for a median period of 80 (range, 24-576) wk and then 7 cases were shifted to an adefovir 10 mg treatment group. All patients had been pre-treated with lamivudine: 5 had YMDD resistant mutants and 6 wild-type virus. When TDF was started, 4 patients had low-level viremia and 6 were PCR-negative.RESULTS: During TDF treatment, PCR remained negative in 10 patients, transaminase levels were normal and no significant viral breakthrough was observed. The drug was well tolerated in all cases. When TDF 75 mg was substituted with adefovir 10 mg, 3 out of 7 patients had a persistent viral rebound (2700-130000 copies/mL),in whom lamivudine had to be reintroduced.CONCLUSION: Low-dose TDF monotherapy can control HBV viremia for an extended period of time without the emergence of resistance and is more potent than adefovir at the standard dosage. The use of a reduced dose of TDF could diminish the cost of therapy in low-income countries, but further studies in a larger population and in HBeAg-positive subjects are needed.