The relationship of immunologic concepts to endodontic diseases is discussed. Immunologic mechanisms are considered, including antigens, haptens, antibodies, and cell-mediated responses. Studies of immunologic manifestations in endodontic diseases are given. These include (1) localization of plasma proteins in inflammed human dental pulp, (2) introduction of microbes into animal root canals, (3) introduction of non-microbial antigens into animal root canals, (4) introduction of root canal antigens into human beings, (5) introduction of root canal antigens into animals, (6) studies of "focal" infection, (7) examination of serum antibodies, (8) examination of periapical lesions, and (9) a cell-mediated study. Next, immunologic concepts related to periapical pathosis are considered. Finally, preventive and treatment concepts are reviewed.