Circumscribed and confined infection, commonly expressed as focal infection, has long been recognized as an important etiologic factor in systemic disease. Yet as a principle it has not received sufficient attention from practitioners. In my opinion focal infection is very frequently related to local and general disease. Apparently it is an important factor in some systemic diseases, heretofore unsuspected. For several years, the medical clinic of Rush Medical College and the Presbyterian Hospital has furnished a large number of patients suffering from chronic infectious endocarditis of the malignant type (Streptococcus viridans), arthritis deformans, rheumatic fever, nephritis acute and chronic, myocarditis chronica, exophthalmic goiter, cholecystitis, ulcer (peptic) of stomach, diabetes mellitus, etc. In addition to the usual clinical and laboratory investigations by the members of the clinic, collective and cooperative research has been carried on in connection with the workers of the Otho S. A. Sprague Memorial Institute and the Memorial