A potent leukocyte chemotactic and activating cytokine, interleukin‐8 (IL‐8), is produced by numerous types of cells in response to inflammatory stimuli. Accumulating evidence indicate that the transcription of IL‐8 gene requires the activation of either the combination of NF‐xB and AP‐1 or that of NF‐xB and NF‐IL6, depending on the type of cells. Alternatively, the activation of NF‐xB is indispensable for IL‐8 gene activation in any types of cells examined. On the other hand, an immunosuppressant, FK506, and a glucocorticoid inhibit the gene transcription as well as the production of IL‐8. Molecular analyses of IL‐8 gene repression by these agents revealed that both affected the activity of the transcription factor(s) bound to the NF‐xB site, albeit in different ways, thereby suppressing IL‐8 gene transcription. Collectively, IL‐8 production seems to be controlled mainly at the activation step of the transcription factor(s) bound to the NF‐xB site. J. Leukoc. Biol. 56: 554–558; 1994.