Interleukin (IL)-10 is a potent immunosuppressant of monocyte/macrophage function and may help control the inflammatory response induced by bacterial infection. To analyze whether IL-10 is detectable in plasma of patients with septic shock and to evaluate its relationship with endotoxin (lipopolysaccharide [LPS])-induced and monocyte/macrophage-induced inflammatory response, plasma IL-10, tumor necrosis factor (TNF)-alpha, IL-1 beta, IL-6, IL-8, LPS, and neopterin were studied in 24 patients with septic shock and in 12 critically ill patients. Eighty-three percent of patients with septic shock and 25% of critically ill patients had detectable levels of IL-10 (P < .001). There was a significant correlation between plasma IL-10, neopterin (r = .72), TNF-alpha (r = .76), IL-6 (r = .68), and IL-8 (r = .61) levels in patients with septic shock. Monocyte/macrophage activation leads to massive secretion of IL-10, which, however, seems to be unable to control the increased production of proinflammatory mediators during septic shock.