In four patients with Philadelphia chromosome-positive (Ph1) chronic myelogenous leukemia (CML), bone marrow hypoplasia (three patients) and aplasia (one patient) developed during or after therapy with either alpha-interferon (IFN) or gamma-IFN. The predominant clinical characteristic of this complication was protracted pancytopenia, which required 2 to 5 months recovery time after treatment and did not resolve in one patient. Bone marrow cytogenetic analysis in two of the patients demonstrated 100% Ph1 metaphases despite the profound bone marrow suppression. Overall, this complication was uncommon, occurring in less than 2% of the patients with CML treated with various IFN. The possible underlying causes include previous therapy with alkylating agents, lack of "reservoir" or normal stem cells, or pronounced sensitivity of the malignant cell clone to the suppressive effect of IFN.