To evaluate the possible usefulness of simultaneous administration of levamisole and interferon, we randomly allocated 38 children with chronic hepatitis B to receive either 10 MU/m2 interferon-α-2a, three times a week for 6 mo (group 1, n = 20) or 90 mg/m2 of levamisole for 45 days, together with 10 MU/m2 of interferon-α-2a, three times a week for 6 mo (group 2, n = 18). At the end of the follow-up period (15 mo), no significant differences were observed between the groups with respect to loss of hepatitis B virus DNA and HBeAg from serum and normalization of serum ALT levels. During therapy, a significant increase in the serum levels of ALT and soluble interleukin-2 receptor was observed in both groups but was higher in patients from group 2. The combination of levamisole with interferon was associated with severe side effects. In summary, the combination of levamisole with interferon in children with chronic hepatitis B does not improve the results obtained with interferon alone. (HEPATOLOGY 1993;18:264–269).