Immediate hypersensitivityreactions were induced in the periodontium and skin of monkeys sensitized with novo alcalase. Animals were challenged in the gingival papillae with 0.1, 1.0, and 10μg of antigen for 1, 3, 5, or 7 consecutive days prior to sacrifice. At the same time, skin sites were challenged with 1μg of antigen. With repetitive immediate hypersensitivity reactions, the inflammatory infiltrate changed from one characterized by polymorphonuclear leukocytes to one characterized by plasma cells and lymphocytes. The repetitive gingival exposure to bacterial antigens which occur in periodontal disease could lead to repetitive immediate hypersensitivity reactions. Such reactions could play a role in the histopathology of human periodontal disease.