Background. Progress in the treatment of B-cell chronic lymphocytic leukemia (CLL) is slow. New investigational agents include alpha-interferon (IFN), which was shown to be active in small series of patients and for a short period of time. Methods. Human recombinant alpha-IFN-2b (INTRON-A) was administered at a dose of 3MU daily for 6 to 12 mo. to 26 patients with early stage and previously untreated CLL, and to 3 previously treated patients. Response (regression to stage 0, or reduction of leukemic cell mass to less than 50%) was evaluated after 6 and 12 mo. Results. 15 of 26 pts. (58%) had a stable response for more than 1 year, 9 (31%) had temporary or minor response, and 2 (7%) had disease progression. In the remaining 3 cases, treatment was discontinued within 3 mo. because of side effects. Conclusions. IFN is effective for long-term treatment and control of early stage CLL and is worth investigating in advanced stage CLL.