Adult periodontitis (AP) is a chronic inflammatory disease of the tooth-supporting apparatus. Activation products of the inflammation-inducing complement system have been detected in the gingival crevicular fluid at the site of gingival inflammation. In the present study, we examined whether evidence for ongoing complement activation in gingival tissues of patients with AP can be obtained. In light of the potential tissue-damaging effects of the complement system, we also examined how the gingival tissue is protected against the cytolytic activity of complement. Surgical and autopsy samples of AP (n = 18) and healthy (n = 11) gingiva were analyzed for the expression or deposition of the complement regulators protectin (CD59) and vitronectin (S-protein) and complement components C3d and C9 by indirect immunofluorescence microscopy with specific antibodies. In healthy gingiva, protection was strongly expressed on the membranes of epithelial cells and on the vascular endothelia of the underlying connective tissue. In AP, protectin was also strongly expressed by endothelial cells, but in the epithelia the expression was granular and weaker than in the healthy gingiva. Coarse granular deposits of complement components were seen in the subepithelial tissues of 61% (C3d), 39% (C9), and 33% (vitronectin) of AP patients, compared with 9% (one case in 11) in healthy controls. In addition, deposits of C3d, C9, and vitronectin were observed on the basement membranes of both pocket and oral epithelium of healthy and AP gingiva but not at sites of protectin expression. The results suggest an increased turnover of the complement system in the gingival tissues of AP patients. The gingival epithelium and connective tissue endothelia are well-protected against damage by the membrane attack complex of complement (MAC). Protection of the underlying connective tissue is insufficient, however, and may allow for deposition of MAC and autologous tissue damage in AP.