Serum concentrations of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-lβ, and IL-6, and the anti-inflammatory cytokine 11–10, and IL-1 receptor antagonists (IL-1ra) and soluble TNF receptors (sTNFRs) were measured in 65 patients with severe sepsis. All patients were evaluated clinically and microbiologically and were followed up for clinical outcome. Levels of both pro- and anti-inflammatory cytokines were significantly elevated in patients with sepsis. Elevated serum IL-10 and TNF-α levels and a high IL-10 to TNF-α ratio were associated with death, whereas higher levels of TNF-α, IL-6, IL-lra, and sTNFR were detected in patients with an early hemodynamic deterioration. Interleukin-10 and IL-10 : TNF-α ratio remained higher in nonsurvivors, whereas IL-10 paralleled the sepsis score. Although both the inflammatory and anti-inflammatory response is profoundly augmented in patients with severe sepsis, the sustained overproduction of the anti-inflammatory cytokine IL-10 is the main predictor of severity and fatal outcome.