The activity and tolerability of a retreatment cycle with leucocyte interferon-alpha (IFN-alpha) (6 million units (MU) three times weekly for 12 months) was evaluated in a group of 22 hepatitis C patients who had been intolerant to a previous course of lymphoblastoid IFN-alpha. Seven patients (31%) discontinued the new therapy owing to either a lack of response (six patients) or to severe leucopenia (one patient). Fifteen patients (68%) completed the 12-month treatment: all had a biochemical response and 10 (45%) also had disappearance of serum HCV RNA (complete response). Mild adverse reactions (fever, headaches and diarrhoea) were seen in these patients during retreatment. After 12 months of follow-up, 11 patients (50%) still maintained the biochemical response (long-term response); seven of these patients (32%) were also negative for serum HCV RNA. Biochemical and complete responses, at the end of both treatment and follow-up, were similar to those seen with lymphoblastoid IFN-alpha. The full dose of leucocyte IFN-alpha, when used in patients previously intolerant to the same dosage of lymphoblastoid IFN-alpha, was better tolerated: only one of the 15 patients who completed the 12-month treatment had a severe adverse event leading to withdrawal vs 22 of 68 patients treated with lymphoblastoid IFN-alpha. Furthermore, there were no manifestations of serological or clinical autoimmunity caused by leucocyte IFN-alpha, even in patients with autoantibodies associated with previous IFN therapy.