The objective of this study was to investigate the possibility of predictive factors of response to treatment with interferon in children with chronic hepatitis B virus infection. We analyzed the influence on the response rate of age, sex, mode of acquisition of infection, severity, and duration of disease in 16 children with chronic hepatitis B treated with 3 MU of recombinant α-interferon 2b three times a week for 6 months. Six months after the end of treatment, eight patients (50%) had cleared HBV DNA, seroconverted to anti-HBe and normalized serum transaminase values. Response was significantly higher in those whose serum transaminase levels were > 100 IU/liter before treatment (70%) and those infected after birth (72%) compared with those with lower serum transaminase levels (16%) and those infected at birth (7%). Our findings indicate that a 6 month course of low dose interferon (3 MU) is highly effective in children with horizontally transmitted chronic hepatitis B virus infection, but noneffective in children infected at birth.