Two patients with chronic-phase chronic granulocytic leukemia initially responded to recombinant interferon alpha-2a (rIFN-alpha-2a) but relapsed as a result of development of hightiter neutralizing antibodies to rIFN-alpha-2a. Both patients were subsequently treated with natural leukocyte IFN-alpha (IFN-alpha-n3), and one of the two patients achieved a durable second hematologic and cytogenetic remission. IFN-alpha-n3 may be considered for patients in whom antibody-mediated resistance to rIFN-alpha-2a develops.