The etiology of a form of periodontal disease in domestic cats known as plasma cell gingivitis-pharyngitis is not understood. Actinobacillus actinomycetemcomitans and Bacteroides species have been strongly implicated as the cause of periodontitis in humans and other mammalian species, and most affected patients manifest serum antibodies reactive with the infecting bacteria. We and others have isolated Bacteroides species from the oral flora of cats. Using enzyme-linked immunosorbent assay (ELISA) and immunoblot procedures, we measured serum antibodies in affected and control cats reactive with human isolates of A. actinomycetemcomitans, B. gingivalis, and B. intermedius, and purified lipopolysaccharide (LPS) from these and other species, and Bacteroides of cat origin. Affected cats had serum antibody titers reactive with these Gram-negative anaerobic bacteria that were significantly elevated relative to those of normal control cats. The quantitatively major antigens recognized by cat serum antibodies are proteins; this contrasts sharply with serum antibodies from humans with juvenile periodontitis, where LPS is the quantitatively major antigen fraction. Our data support the idea that plasma cell gingivitis-pharyngitis in cats may have a bacterial etiology, and that Gram-negative anaerobes similar to those that cause periodontitis in humans and other mammals may be involved.