Recent reports have shown that interferon alpha is effective in B-chronic lymphocytic leukaemia (B-CLL). In a previous study from our unit we obtained a 50% response rate with interferon alfa-2b in B-CLL in early stages. Subsequently, we performed the present study randomizing 34 Binet stage AI, B-CLL patients who were not previously treated (eight controls and 26 who were to receive interferon alfa-2b (IFN alpha-2b) (Intron-A) according to a randomized schedule as follows: 1.5 MU/d in eight patients, 1.5 MU three times a week in 10 patients and 3.0 MU three times a week in eight patients). At 3 months complete response (CR) was obtained in one, partial haematologic response (PHR) in nine and minor haematologic response (MHR) in seven patients with an overall response rate 17/26 or 65%. No bone marrow changes regarding the pattern or degree of infiltration was noticed in any of the responding patients except for the complete responder. Treatment was continued in 15 patients (reduced to two-thirds of the initial dose in the PHR and to one third of the initial dose in the MHR) while in 11 patients it was discontinued because of no response, negative response or toxicity. At 6 months sustained response was observed in 10 patients, while in the remaining five an increase of blood lymphocytes was seen at numbers similar or higher to those noted prior to interferon alfa-2b therapy. Two of the 10 patients in whom blood lymphocytes were still reduced to less than 50% of the pretreatment values, developed gradual lymph node enlargement and therapy had to be discontinued. During the following 6 months the interferon alfa-2b dose was further reduced in all remaining responders to 1.5 MU once or twice a week and their counts remained at the same level as at 6 months of therapy. At 12 months, 18 of our patients were still in stage A while seven had progressed (five to stage B and two to stage C). The overall response after 12 months of therapy was sustained in 8/17 responders. We conclude from our study that interferon alfa-2b is effective in untreated B-CLL patients in early stages and therefore should be investigated in combination with conventional chemotherapy. Clinical trials utilizing interferon alfa-2b and chlorambucil in combination in untreated B-CLL patients are currently in progress in our unit.