Lamivudine, an oral nucleoside analogue, is a potent inhibitor of hepatitis B virus (HBV) replication. The decision to initiate therapy should be based on variables which are predictive of lamivudine-induced HBeAg loss. The aim of this study was to identify the predictive factors of responsiveness to lamivudine treatment in children with chronic hepatitis B. Lamivudine, 3 mg/kg/day (maximum, 100 mg/day), was given to 39 children with chronic HBV infection for more than 6 months. We retrospectively analyzed the effects of baseline factors on virologic response, which was defined as the loss of HBeAg and HBV DNA after cessation of therapy. Univariate and multivariate analyses examined the effects of lamivudine treatment, age, gender, duration of treatment, previous interferon therapy, maternal HBsAg state, baseline alanine aminotransferase (ALT) and HBV DNA level. Serum HBeAg and HBV DNA became negative in 20 (51.3%) out of 39 children at the time of cessation of lamivudine treatment. In the univariate analysis, higher baseline ALT and lower HBV DNA level were independently associated with a favorable response to lamivudine treatment (p<0.05). Multivariate regression analysis showed that elevated baseline ALT was the best independent predictor of response to lamivudine treatment (p<0.05). Virologic response of lamivudine could be expected in the half of children with chronic HBV infection. Children with elevated pretreatment ALT levels were most likely to respond to lamivudine treatment.