The role played by alpha interferon (alpha-IFN) in the treatment of B-type chronic lymphocytic leukaemia (B-CLL) has been studied by different authors. Despite the inconclusiveness of the results, alpha-IFN seems to be more effective in those patients with low tumour burden (early stages) who have been previously untreated. Although the mechanism of action of alpha-IFN is not wholly understood, it is known that this agent is a strong stimulant of the natural killer lymphocytes (NK). NK activity has been found decreased in B-CLL. In the present work the effect of alpha-IFN on NK activity was studied in 9 previously untreated B-CLL patients in stage A, who received chlorambucil (CLB) followed by alpha-IFN for at least 4 months. The disease stage did not change in most of the patients during alkylating or IFN therapy. CLB failed to increase NK activity, although it diminished the lymphocyte count. Although the lymphocyte count of the patients treated with alpha-IFN was not reduced beyond the values attained by CLB, NK activity reached normal values in 5 of the 7 patients in whom this was low, and kept within normal ranges in the two patients with normal NK activity. The number of CD57+ lymphocytes (this being the antigen present in NK cells) increased after alpha-IFN treatment, without any changes in the remaining T-lymphocyte (CD2, CD4 and CD8) and NK (CD16 and CD11b) subpopulations. These results show that alpha-IFN enhances NK activity in vivo.