Fusidic acid, a tetracyclic triterpenoic acid, is used for local and systemic treatment of bacterial infections. Its in vitro effects on the human immune response were tested. Activated blood mononuclear cells released lower levels of interleukin (IL) 1 in the presence of nontoxic and clinically attainable levels of fuscidic acid (15 to 50 micrograms/mL). In contrast, the drug failed to affect the production of two other monocyte-derived cytokines, tumor necrosis factor (TNF)-alpha and IL 6. The production of the T-cell-derived cytokines, IL 2 and interferon-gamma (IFN-gamma), were also suppressed (IC50: 5 to 15 micrograms/mL). The early costimulatory effects of IL 1 and IL 6 on mouse thymocytes and human T cells were suppressed by similar levels of the drug, as was the hybridoma growth-promoting function of IL 6. T-cell proliferation induced by phytohemagglutinin or allogeneic cells was reversibly inhibited (IC50: 15 micrograms/mL). These functions of fusidic acid were strikingly similar to those of cyclosporin A. Because of the low toxicity of the former, it may have a role as a clinically useful suppressor of immunoinflammatory processes.