Thirty-five children with chronic hepatitis B were randomly assigned to three groups: group 1 (n = 12), untreated; group 2 (n = 11), treated with 1 million units of interferon gamma per square meter of body surface (MU/m2), three times a week for 24 weeks; and group 3 (n = 12), treated with interferon alfa at a dose of 5 MU/m2, three times a week for 12 weeks followed by 1 MU/m2 of interferon gamma with the same schedule. At the end of the treatment (6th month), hepatitis B virus DNA was negative in 16.5% of the control group, in 9% of the children treated with interferon gamma, and in 16.5% of those treated with interferons alfa and gamma. No child had lost the hepatitis B e antigen by this time. No basal differences in the serum hepatitis B virus DNA concentration among the groups were observed. At follow-up (15th month), viral genome was negative in 25% of the untreated children, in 36% of the group treated with interferon gamma, and in 41.5% of the children who had received interferons alfa and gamma. Hepatitis B e antigen was negative in 25% of the children who belonged to groups 1 and 3 and in 27% of the children treated with interferon gamma only. These data suggest that interferon gamma does not have a powerful antiviral effect on chronic hepatitis B in children. However, it is well tolerated.