To compare the efficacy and safety of interferon a-1b and interferon a-1b combined with lamivudine in the treatment of HBeAg positive chronic hepatitis B (CHB), to analyze the impact of variable factors on the efficacy, and to investigate the individualized anti-viral regimen for CHB patients. 111 CHB patients were enrolled and randomly divided into two groups. Group A: patients received interferon a-1b (49 patients, 50mug I. M. , qod. ) , Group B: interferon a-1b (idem) combined with lamivudine for 6-12 months or longer(62 patients, 100 mg, P.O. , q.d. ). (1) The HBeAg seroconversion rates of treatment by 12 and 18 months were 28.6% and 36.7% in group A, 29.0% and 38.7% in group B, respectively, no significant difference found between the two groups at the end of treatment (x2=0.003, P value is more than 0.05; x2=1.500, P value is more than 0.05). (2) The HBV DNA undetectable rates of treatment by 6 months, 12 months and 18 months were 8.2%, 53.1% and 57.1% in group A, 66.1%, 83.9% and 88.7% in group B, respectively, still no significant difference existed between the two groups (x2=38.150, P value is less than 0.05; x2=12.073, P value is less than 0.05, x2=14.459, P value is less than 0.05). (3) In group A, the HBeAg seroconversion rates for male and female patients were 34.5% and 40.0% respectively, no significant difference found between. As regard ages the rates were 34.9% and 50.0% for patients younger or more than 40 years of age, no significant difference existed between. The HBeAg seroconversion rate was higher in patients with lower baseline serum HBV DNA loads ( less than 6 log10 copies/ml) . (4) The rates of patients with fever and blood abnormality were 36.7% and 34.7% in group A, 32.3% and 27.4% in group B, respectively. The total incidences of adverse events were similar between group A and B (x2=0.244, P value is more than 0.05; x2=0.682, P value is more than 0.05). (5) The ratio of drug resistance in group B was only 1.6%. The adverse events of interferon a-1b treatment for CHB are low and mild. The HBeAg seroconversion rate persistently raises with the extension of interferon a-1b treatment course. The HBV DNA undetectable rate of interferon a-1b combined with lamivudine is significantly higher than that of interferon a-1b and the drug resistance of lamivudine can be reduced obviously by combination therapy.