The in vivo activity of soluble antigen-antibody complexes was tested by a single intradermal injection in rabbits. Skin reactions were obtained marked by erythema, induration, and occasionally hemorrhage and necrosis. Microscopically, diffuse inflammation and occasional vascular necrosis could be found at all dosages. This indicates that soluble antigen-antibody complexes are phlogogenic and provides support for the suggestion that complexes are responsible for the lesions seen in serum sickness. The reactions were similar in severity to local passive Arthus (LPA) reactions at equal dosages of antibody in the dosage range studied. BSA antigen could be found in large concentrations in affected vessel walls of both reverse passive Arthus (RPA) and active or classical Arthus reactions. It is suggested that this predominantly vascular localization of antigen might bring about the relative severity of the RPA and active Arthus reactions, as contrasted to the complex and LPA reactions. The finding of affected vessels in the complex and LPA reactions containing little or no antigen and antibody, while these components were present in adjacent areas, suggests that the antigen-antibody combination may cause vascular reaction and damage by the release of physiologically active mediators from the tissue or tissue fluid.