The two chemotactic cytokines interleukin-8 (IL-8) and epithelial neutrophil activating protein 78 (ENA-78) were recently shown to be potent chemoattractants and activators of neutrophil function and to be present in certain inflammatory diseases. We have studied the effects of recombinant and natural interferon-α (IFN-α) and of recombinant interferon gamma (rIFN-γ) on the production of EL-8 and ENA-78 in lipopolysaccharide- and interleukin-1–stimulated human monocytes. Both types of interferons showed a strong, concentration-dependent inhibition of neutrophil-stimulating bioactivity. Similarly, the secretion of IL-8 and ENA-78 was also inhibited by up to 73%. Northern blot experiments demonstrated that IFN-α decreases the steady-state levels of IL-8 and ENA-78 mRNA in monocytes, suggesting that IFN-α as well as IFN-γ may control the expression of neutrophil chemotactic cytokines at the mRNA level. J. Leukoc. Biol. 57: 929–935; 1995.