Superoxide dismutase or derivatives thereof have been shown to be potent anti-inflammatory agents in several models of induced inflammation. In all cases, the anti-inflammatory effects included a marked suppression of the accumulation of inflammatory cells at the site of the potential lesion, suggesting a role for the superoxide radical in the chemotaxis process. The exposure of normal plasma to a source of superoxide in vitro resulted in the formation of a powerful chemotactic factor for human neutrophils. The factor is activated by reacting specifically with superoxide, and was found to consist of a complex of serum albumin and an unidentified lipid. The complex may be resolved and reconstituted. Both components are required for expression of biologic activity. The major mechanism for the anti-inflammatory activity of superoxide dismutase appears to be the prevention of the formation of this plasma-derived superoxide-dependent chemotactic factor.