Purpose: To identify the predictive factors of long-term therapeutic response or resistance to lamivudine treatment in children and adolescents with chronic hepatitis B. Methods: Eighty one children and adolescents with chronic hepatitis B were included, who received lamivudine treatment for at least 6 months. Their condition was monitored for at least 12 months (12-88 months) thereafter. Twenty one (25.9%) were preschool children ($age{leq}6$). For patients who had developed HBeAg seroconversion or breakthrough, univariate and multivariate analyses were used to identify the effects of age, gender, pretreatment alanine aminotransferase (ALT) and hepatitis B virus DNA levels. Results: HBeAg seroconversion occurred in 49 (60.5%) of the 81 patients after the initiation of the lamivudine therapy. In 65 patients whom were monitored for over 24 months, the seroconversion rate was significantly higher in younger patients (p=0.040), especially in those patients of preschool age ($age{leq}6$, p=0.031). The seroconversion rate was significantly higher in higher pretreatment ALT (p=0.003). The breakthrough occurred in 21 (25.9%) of the 81. The breakthrough rate was lower in younger aged patients ($age{leq}6$), and with higher pretreatment ALT levels, but no significant difference. Conclusion: Younger age is a good predictor of HBeAg seroconversion in children with long-term lamivudine treatment as well as high pretreatment ALT levels.