AFTER AN IMMUNOGENIC STIMULUS, antibodiesare produced that combine with the evoking antigenic determinants wherever they are encountered, thereby forming immune complexes (ICs). This process is usually of benefitto the host, since it results in the neutralization or elimi-nation of the antigens. However, ICs may, under certain conditions, local-ize in vascular structures, thereby inciting phlogogenic responses. The localization may result either from formation of the complex at the site as in the Arthus reaction or from deposition of circulating ICs. It is this latter circumstance, in which complexes from the circulation produce lesions in multiple sites, thatis generally referred to as" immune complex disease." Research has recently clarified many factors involved in the formation, removal, and localization of ICs and the mechanisms of IC-induced biologic functions as well as inflammatory reactions. ICs have assumed the role of regulatory factors in immune responses, because they can interact with antigen receptor-bearing lymphocytes and subpopulations of T and B cells, as well as unclassified lymphocytes and macrophages havingFc and complement (C) receptors. Additionally, as IC-mediated biologic ac-tivities and immunopathologic consequences become clearly established and new techniques for demonstrating ICs in tissues and biologic fluids are developed, considerable evidence substantiates the primary pathogenic significance of ICs in a variety of animals and human diseases. It was originally von Pirquet 1 who drew analogies between the immunologic and clinical events in the serum sickness of men and laboratory animals, in both cases presumably caused by antigen-antibody reactions, and the manifestations of various infectious diseases. Confirmation and amplification of von Pirquet's theory followed 50 years later with the experimental model of" one shot" serum sickness, in which the onset of glomerulone-phritis and generalized vasculitis coincided with the appearance of soluble ICs in the circulation of rabbits injected once with a sizable antigenic