18 patients with early stage, previously untreated B-CLL were given interferon alfa (IFN alpha) 2a. 3 MU thrice weekly, subcutaneously. The peripheral lymphocyte count decreased in all patients. Response was delayed in three patients until they had received a median of 5 months therapy, one of whom had an initial transient increase in lymphocytes. Two patients normalized their blood lymphocyte counts, but neither achieved complete remission (CR). Responses were transient in eight patients lasting a median of 5 months (3-21). Binding anti-IFN alpha antibodies were present in 9/17 patients tested (53%). Low titre binding antibodies (< 533 IBU/ml) were not associated with LHR, but high titre antibodies (> 4401 IBU/ml) were. Two of 12 patients assessed had a > 3 g/l increase in baseline serum IgG levels during IFN alpha therapy, one of whom reverted to pretreatment levels in association with LHR. Haematological toxicity was moderate, other than in two patients, one of whom developed autoimmune haemolytic anaemia and the other thrombocytopenia. We conclude that IFN alpha lowers the lymphocyte count in early stage CLL, that the response may be delayed and that anti-IFN alpha antibodies may play a role in a proportion of those in whom the response is transient.