The pattern of complement component utilization within the joint space of patients with RA is consistent with activation by immune complexes. Immunogluorescent studies of SF leukocytes revealed intracytoplasmic inclusions of immunoglobulins and complement components, particularly in cells from SF with low complement levels and containing materials which precipitated with either C1q and/or rheumatoid factor. RA patients with low levels of SF complement tended to have an unremitting course, subcutaneous nodules, and to have been treated with gold. Their joints had more periarticular demineralization, joint space narrowing, cortical impaction by X-ray; and synoviocytic giant cells, fibrosis, lymphocytes, congestion, and fibrin exudation by pathologic examination than did joints of RA patients without low levels of SF complement. Patients with systemic hypocomplementemia had active classical RA with evidence of severe joint involvement and vasculitis. These findings suggest that rheumatoid inflammation of joints is mediated by immunologic activation of the complement system.