The mode of action of glucocorticosteroids as immunosuppressive and antiinflammatory agents is not fully understood. Glucocorticosteroids block synthesis of interleukin 1 by interfering with the transcription of the IL-1 beta gene. Glucocorticosteroids may also induce rapid degradation of IL-1 mRNA. In the presence of antigen, IL-1 is a potent accessory-cell-derived growth and differentiation co-factor for stimulating resting T lymphocytes. The recently defined interleukin 6 protein is even more powerful than IL-1 in promoting T cell growth and differentiation and acts synergistically with IL-1. Like IL-1, IL-6 is produced by accessory cells and exhibits pleiotropic functions. We herein describe the effects of glucocorticosteroids on IL-6 synthesis. We provide evidence that glucocorticosteroids prevent IL-6 gene transcription in human peripheral blood mononuclear cells.