Excessive synthesis of proinflammatory cytokines [tumor necrosis factor (TNP)-alpha and interleukin (IL)-1 beta] after trauma has been correlated with poor outcome, Recently, naturally occurring inhibitors of TNF-alpha and IL-1 beta have been characterized such as soluble TNF receptors (sTNFRs) and IL-1 receptor antagonist (IL-1ra), The present study was undertaken to determine whether injury results in a rise of circulating sTNFRs and IL-1ra, If so, whether plasma levels of these anti inflammatory mediators correlate with severity of injury and clinical outcome of these patients, Injured patients (n = 213) showed significantly increased sTNFR and IL-1ra plasma levels throughout the observation period of 14 days, compared with healthy volunteers (n = 127), Patients with severe injury (Injury Severity Score > 16 points) revealed higher levels (p < 0.05) of sTNFRs and IL-1ra than patients with minor trauma (Injury Severity Score less than or equal to 16 points), Patients who died from injury demonstrated increased (p < 0.05) sTNFR p55 and IL-1ra plasma levels, compared with survivors. Thus, anti-inflammatory mechanisms are activated after trauma dependent on severity of injury, Because increased plasma levels of anti-inflammatory reacting proteins portended poorly for patient survival, these mediators may contribute to prediction of outcome after severe injury.