In a prospective, randomized trial, recombinant human superoxide dismutase (rhSOD, 3000 mg/day, Grünenthal, Aachen, Germany) or placebo was given intravenously during 5 days after multiple injuries (Injury Severity Score [ISS] > or = 27; 24 patients). Manifestation of multiple organ failure (MOF) and posttraumatic inflammatory response were evaluated over 14 days. No side effects were noted by continuous infusion of rhSOD, which allowed high SOD plasma levels (24.77 +/- 9.43 mg/L) compared with controls (0.03 +/- 0.02 mg/L). Multiple organ failure was attenuated by rhSOD treatment in respect to cardiovascular and pulmonary functions. Additionally, intensive care therapy was shortened from 30 days (Q25: 15; Q75: 37) to 21 days (Q25: 12; Q75: 41). A secondary increase of inflammatory mediators (e.g., C-reactive protein, polymorphonuclear [PMN]-elastase, phospholipase A2), as observed at the end of the first week in the placebo group, was reduced by rhSOD therapy. The results reveal an attenuation of organ failure after trauma, most likely by decreasing the release of inflammatory mediators and reduction of leukocyte-mediated organ injury. These preliminary results, while promising, need to be confirmed in a larger number of patients.