We treated 114 Ph'+ chronic myeloid leukemia (CML) patients, 105 of whom were in chronic phase (CP) and 9 in accelerated phase (AP), with interferon alpha-2b (IFN alpha-2b) at intermittent or daily doses of 2-5 MU/m2. Of 35 previously untreated CP patients, 22 (63%) showed complete hematological response (CHR). This was significantly influenced by initial risk status. In 19 of the 22 CHR patients the median of Ph'+ cells decreased from 100% to 58%. Of 36 patients pretreated for less than 12 months, 19 (53%) achieved CHR. CHR rate was significantly related to IFN dose. Cytogenetic improvement was observed in 15 of the 19 patients, the median of Ph'+ cells dropping from 100% to 76%, with complete suppression of the Ph' chromosome in 1 case. Of the 34 patients pretreated for greater than 12 months, 21 (62%) obtained CHR. Cytogenetic improvement was observed in 10 cases, the median of Ph'+ cells declining from 100% to 66%. 1 of 9 AP patients obtained CHR. After a median follow-up of 32 months for the 63 CHR patients, 49 (78%) are still in disease control: 34 on IFN therapy, 15 after bone marrow transplantation (BMT) (13 autologous and 2 allogeneic). Blastic transformation (BT) occurred in 9 of 63 (14%) CHR patients and in 24 of 51 (47%) patients with less than CHR. IFN alpha-2b has proved to be an effective treatment for CML. Its combination with other treatment modalities represents an interesting and promising approach for future studies.