The authors report two patients with characteristic features of chronic neutrophilic leukemia (CNL) treated with alpha-2b-interferon (IFN) (Schering-Plough). At initiation of therapy, both patients had progressive disease and presented with large tumors. A rapid reduction of the tumor mass and a long-term stabilisation of the myeloproliferative disorder was obtained (therapy duration 16 and 26 months, respectively, and presently ongoing). In one patient, the dose of IFN could be significantly reduced during maintenance without relapse. Neither presented infectious or hemorrhagic complications under therapy. Alpha-2b-interferon is active and safe in CNL, even pretreated and progressive. It can also correct the neutrophil and natural killer functional defects frequently observed in CNL.