To determine in vivo effects of interleukin (IL)-12 on host inflammatory mediator systems, 4 healthy chimpanzees received recombinant human IL-12 (1 μg/kg) by intravenous injection. IL-12 induced increases in plasma concentrations of IL-15, IL-18, and interferon-γ (IFN-γ), plus a marked antiinflammatory cytokine response (IL-10, soluble tumor necrosis factor [TNF] receptors, IL-1 receptor antagonist) and secretion of α-chemokines (IL-8, IFN-γ—inducible protein 10) and β-chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1β). In addition, IL-12 elicited neutrophilic leukocytosis, neutrophil degranulation (elastase-α₁-antitrypsin complexes), coagulation activation (F1 + 2 prothrombin fragment, thrombin-antithrombin III complexes), and fibrinolytic activation (tissue-type plasminogen activator, plasmin-α₂-antiplasmin complexes). IL-12—induced activation of multiple host mediator systems was found only after 8–24 h, remained detectable until the end of the 48-h observation period, and occurred in the absence of detectable TNF and IL-1b. These data may contribute to understanding the role of IL-12 in the pathogenesis of sepsis syndrome and the toxicity found after repeated injections of IL-12.