Summary We assessed the efficacy of prolonged interferon-α (IFN) therapy in children with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26 paediatric cases with IFN-α2b(5 MU m-2, then 3 MU m-2 three times weekly for 12 (medium-term group, MTG) or 24 months (long-term group, LTG). Compliance and tolerability were acceptable. At the end of therapy a complete biochemical response [normalization of alanine aminotransferase (ALT)] occurred in 12 children (5/13 in MTG and 7/13 in LTG). A relapse occurred after stopping IFN in 10 cases (five in MTG and five in LTG). Two patients from the LTG had normal liver function tests during 12 months of follow-up. Six of the eight hepatitis Be antigen (HBeAg) positive children lost HBeAg, while all six hepatitis B virus (HBV) DNA positive patients lost HBV DNA during treatment. HBeAg reappeared later in two children. HDV RNA, present in 10/10 cases of MTG before treatment, persisted after 12 months IFN therapy in 3/10. One year after stopping therapy, 8/10 patients were again HDV RNA positive. Two children cleared hepatitis delta antigen (HDVAg) from the liver. No significant improvements in liver histology were seen in both groups. Our experience suggests that IFN-α treatment in children with chronic type D hepatitis has a transient effect, and long-term treatment does not appear to induce a greater therapeutic benefit in terms of biochemical and virological response.