Summary. There are few reports on hepatitis B e antigen (HBeAg) titres during nucleos(t)ide analogues treatment. We investigated the changes in HBeAg levels in patients treated with entecavir and the usefulness of HBeAg quantification for predicting antiviral response. Ninety-five consecutive HBeAg-positive patients treated with entecavir for more than 48 weeks were enrolled. Serum levels of hepatitis B surface antigen (HBsAg), HBeAg and HBV DNA were assessed at 4-week intervals to week 24 and thereafter at 12-week intervals. Virologic response (Y1VR) was defined as an undetectable HBV DNA level at week 48 of therapy. During 48 weeks, HBeAg and HBV DNA level decreased significantly in a biphasic manner and HBsAg level tended to decease. Fifty-three patients (55.8%) attained Y1VR. Pretreatment HBeAg levels were significantly lower in the Y1VR group than in no Y1VR group. At week 4 and 12 of therapy, 25% and 41.4% of patients showed a decrease of HBeAg levels with >0.5 log10 and >1.0 log10 from baseline, respectively. These patients achieved more Y1VR than those with less decrease of HBeAg levels (97.7%vs 22.2% and 86.2%vs 29.3%, respectively). HBeAg level at week 12 had higher predictive values for Y1VR than HBV DNA level. Multivariate analysis revealed that a pretreatment HBeAg level of <360 PEIU/mL and the reduction in HBeAg level >1.0 log10 at week 12 were associated with Y1VR. These results suggest that pretreatment HBeAg level and an early decrease in HBeAg level are useful measurements for predicting one-year virologic response during entecavir treatment.