OBJECTIVE To observe viral dynamic change in patients with HBeAg positive chronic hepatitis B by lamivudine treatment. METHODS A multi-center clinical trial. Both outpatients and inpatients with HBeAg positive chronic hepatitis B have been administrated lamivudine 100 mg/d for 24 weeks. To detect the hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels of the baseline, 12 hours, 1 day, 2 days, 3 days, 1 week, 2 weeks, 4 weeks, 12 weeks, 24 weeks after lamivudine treatment by real time polymerase chain reaction (PCR). To estimate the parameters of viral dynamics through regression analysis. RESULTS 172 patients were enrolled, 145 male, 30.8 +/- 9.7 (16 - 65) years old. Significant decrease of HBV DNA level occurred 12 hours after administration, the average decrease was 0.45 lg(copies/ml), maximum was 3.86 lg(copies/ml), 4 patients decreased not less than 2 lg(copies/ml). On day 2 and 7, the average decrease was 1.20 lg(copies/ml) and 2.01 lg(copies/ml), maximum was 4.41 lg(copies/ml) and 5.79 lg(copies/ml), respectively. Then HBV DNA level continued decreasing until week 24. 24-week administration of lamivudine cause 4.10 lg(copies/ml) decrease of HBV DNA averagely and 6.68 lg(copies/ml) mostly. Half life of free virion was 2.57 days. Half life of infected hepatocyte was 63.0 days. CONCLUSIONS Lamivudine could rapidly decrease the HBV DNA level of patients with HBeAg positive chronic hepatitis B rapidly.