Monocytes/macrophages are efficient producers of alpha interferons (IFN), and IFN-gamma is a potent activator of these cells, The present study sought to investigate whether IFN-alpha affects the capacity of human monocytes/macrophages to produce IFN-alpha on induction with Sendai virus, Plastic-adherent human peripheral blood monocytes were grown in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) for 3 weeks during which they were transformed into macrophages. At various times, the cultures were pretreated for 24 h with IFN-gamma and induced with Sendai virus for IFN-alpha production, Pretreatment with IFN-gamma had no effect on the production of IFN-alpha during the first days in culture, The production of IFN-alpha was thereafter significantly enhanced by the IFN-gamma pretreatment, Minute amounts of IFN-gamma, less than or equal to 0.1 IU/ml, increased the production of IFN-alpha in macrophages cultured for more than 7 days, The cooperation between IFN-gamma and IFN-alpha in macrophages may play a role in the antiviral defense of the body.