An individual's iron status may affect the response rate achieved with the use of interferon (IFN) as therapy for chronic viral hepatitis. A total of 27 patients with chronic hepatitis B viral infection, who had elevated serum ferritin levels, were randomized to receive either IFN 5 MU, three times weekly by subcutaneous injection alone (n = 14) or in combination with cycles of deferoxamine at a dose od 80 mg kg-1 per cycle (n = 13) administered over 3 consecutive days, to reduce their iron and maintain a serum ferritin level less than 250 ng ml-1. All deferoxamine-treated patients were on a low iron-containing diet. An IFN response was defined as a normalization of the serum alanine aminotransferase (ALT) level and seroconversion from hepatitis B e antigen (HBeAg) positivity to hepatitis B e antibody (HBeAb) positivity. The deferoxamine-treated group experienced a reduction in their serum ferritin level to 226 +/- 73 ng ml-1 as a result of the deferoxamine treatment. Six of the 13 (46%) deferoxamine-treated patients and two of the 14 (14%) control patients normalized their ALT levels. Seven of the 13 (54%) deferoxamine but only 14% of the IFN-treated group seroconverted to HBeAb positivity. A greater rate of histological improvement and loss of hepatitis B virus (HBV) DNA was seen in the deferoxamine-treated group. Two of the deferoxamine-treated patients were treated only once, two were treated twice, seven were treated three times and two were treated four times to achieve a ferritin level below 250 ng ml-1. Based on these data, we conclude that deferoxamine infusion enhances the rate of response to IFN in subjects with chronic hepatitis B. The precise mechanism of this phenomenon is not clear.