Interferon (IFN) has been described to influence various cellular functions. In this study we investigated whether the oxidative response of polymorphonuclear leukocytes (PMN) is also affected by IFN. In order to exclude the possible influence of impurities in IFN preparations, only recombinant human IFN a2 or y were used. Lucigenin-dependent chemiluminescence (CL) of PMN was measured to assess the production of oxygen radicals. IFN 7 at a concentration of more than 10 ng/ml elicited a minimal CL response in PMN. When PMN were incubated with IFN 7 for 1 h and then stimulated with chemotactic peptide f-met-phe (FMP), zymosan-activated serum (ZAS), zymosan particles, or phorbol-myristate acetate (PMA), the CL response was increased as consequence of the generally enhanced oxidative metabolism. IFN a2 showed no such effect at any concentration tested. A 5-min pretreatment with IFN 7 decreased the ZAS response but did not affect the reaction to the other stimuli. The possibility of a generation of IFN by PMN during the assay could he excluded as no IFN activity could be detected in an antiviral assay after stimulation of PMN for 6 h with PolyI• LPS, ConA, C. parvum, PMA, zymosan, or FMP. The modulation of granulocyte activity by IFN 7 may be important in the regulation of the anti-inflammatory response of PMN.