To investigate the factors which may affect the rate of HBeAg seroconversion and its durability after long-term lamivudine therapy in chronic hepatitis B patients.81 patients were treated in a phase III clinical trial with lamivudine 100 mg daily for up to 5 years. The mean period of treatment was (48.84+/-10.52) months (range: 16 approximately 60 months). When HBeAg seroconversion occurred in the patients, which was defined as loss of HBeAg and detection of anti-HBe antibody, HBV DNA level less than 10 mEq/ml more than two times (once every 3 months), the lamivudine treatment was stopped and they were followed-up for another 6 approximately 12 months. The HBV DNA level was detected using Branched DNA assay (Chiron). The HBV markers were detected using IMX assay (Abbott). HBV genotyping was performed using type-specific PCR. The data were analyzed using logistic multivariant analysis.(1) The distribution of HBV genotypes was as follows: type B, 17 (20.97%), type C, 62 (76.54%), and type B+C, 2 (2.47%). (2) 26 patients achieved HBeAg seroconversion (32.10%). The annual seroconversion rates were 16.05% (13/81) in the 1st year, 19.75% (16/81) in the 2nd, 27.16 % (22/81) in the 3rd, 28.40% (23/81) in the 4th and 32.10% (26/81) in the 5th year. Four patients had a reappearance of HBeAg and an elevation of HBV DNA. Therefore the stability ratio was 84.62% (22/26). The mean baseline ALT and HBV DNA levels in those who were seroconvered were (104.8+/-86.3) U/L and (940.1+/-1123.7) mEq/ml, respectively. Mean baseline ALT and HBV DNA of non-seroconverters were (48.3+/-46.9) U/L and (2152.3+/-3063.5) mEq/ml. There was a significant difference between the two groups shown by Kruskal-Wallis Test (P < 0.05). Analysis by logistic multivariate analysis showed that the rate of HBeAg seroconversion and its durability rate correlated with a high baseline ALT. In contrast, a relatively low seroconversion rate and durability rate was observed in patients with high baseline HBV DNA. The durability rate also correlated with additional lamivudine treatment after HBeAg seroconversion.Continuation of lamivudine therapy for more than 6 months after HBeAg seroconversion might increase the durability of response.