This study aimed at evaluating the effectiveness of alpha interferon (IFN) in chronic myelomonocytic leukemia, a disease for which therapeutic options are still unsatisfactory. Fourteen sequential unselected patients received recombinant alpha-2b IFN (Intron-A, Schering-Essex) 3 megaU/day, progressively elevated to 10 megaU/day in non responders. Rate and type of response were evaluated in the 10 patients who completed a minimum treatment period of three months. Monocytosis, present in all patients by definition, was reduced in 8 of these 10; neutrophils decreased in 5 of 7 patients with high initial values. Signs of ineffective hemopoiesis were generally not influenced by the treatment, nor were organomegaly and hypergammaglobulinemia, when present; however, in 4 patients the Hb level improved with treatment. IFN treatment failed to improve in vitro growth of GM colonies, but there was improvement of the cluster/colony ratio, due to decrease number of clusters. Lysozyme production by pathologic monocytes was inhibited in the presence of IFN in vitro. Tolerance was variable: three patients interrupted the treatment for unmanageable side effects. These results show that alpha IFN can be effective in CMML patients with prominent proliferative aspects.