Abstract: Objective To investigate the clinical significance of YMDD mutation during Lamivudine therapy on chronic hepatitis B.Methods Fluorometric analysis PCR, ELISA were used to estimate the YMDD mutation, HBVDNA quantative level and HBeAg for HBV of 72 cases with chronic hepatitis B before therapy (0 month) , and after Lamivudine therapy for 9, 12, 18 months.Results The YMDD mutation was not observed in these cases before Lamivudine therapy.The mutation was found in 8 cases (11.1%) , 17 cases (23.6%) and 28 cases (38.9%) at 9, 12, 18 month for therapy.The YMDD mutation rate rose with the therapy time lasting (P<0.05) .Moreover, the YmDD mutation rate in the patients with HBVDNA quantity higher than 108 copies/ml was significantly higher than that in the patients with HBVDNA quantity lower than 108 copies/ml (P<0.005) .The YMDD variation rate in patients with HBeAg positive and in patients with HBeAg negative showed no significant difference (P>0.05) .The HBeAg negative conversion rate was significantly higher in non-mutation group than that in mutation group (P<0.05) .Conclusion The serum virus quantity may be regard as an early estimate indication of the development of YMDD mutation during Lamivudine therapy.