These studies were made for the purpose of finding out the relationship of periodontosis to histamine and the etiologic factors of the disease since the pharmacological action of histamine is very similar to the inflammatory state of periodontosis. The results obtained are summarized as follows: 1) Gingivae of 51 cases of periodontosis showed a threefold increase in histamine, compared with those of 20 control cases operated surgically in the oral cavity. It is suggested by these results, in conjunction with the histopathological observations, that periodontosis has a certain relationship to allergy. 2) In cases of periodontosis an increase in mast cells and their morphologic changes were noticed in the microscopic specimens when stained with a one per cent solution of toluidine blue. These findings are known to be positively correlated with an increase of histamine. 3) In the animal experiments an increase of gingival histamine could not be attributed to physico-chemical stimulation alone and it was not noted when a local anaphylaxis (allergy) was induced. However, it became particularly marked when the local anaphylaxis was compounded by the above-mentioned strong stimulation. These animals showed both macroscopic and microscopic changes suggestive of periodontosis. 4) In slight or early cases of periodontosis favorable results were obtained by topical applications of sinomenine and an anti-histamine ointment which were administered in order to eliminate excessive amounts of histamine in the gingiva. Therefore it may be concluded that periodontosis has a close relationship to histamine and allergy.