Circulating immune complexes (CICs) are a heterogeneous group of immunoreactants formed by the noncovalent union of antigen and antibody. Many factors influence the formation, immunochemistry, biology, and clearance of these soluble reactants. The recent development of sensitive assays for the detection of CICs and the capability to assess immune complex (IC) clearance mechanisms in humans in vivo have expanded our understanding of these mediators. CICs influence both the afferent and efferent limbs of the immune response and can mediate tissue damage in certain pathologic states. ICs probably play an important role in the pathogenesis of serum sickness, systemic lupus erythematosus, and cutaneous necrotizing vasculitis. Recent investigations have raised the possibility that CICs may be of significance in other types of vasculitis as well. In other instances, ICs may form in response to tissue injury and subsequently modify the immune response of the host. A review of this material with special emphasis on diseases of relevance to dermatologists is presented.