In view of the manifold therapeutic effects of glucocorticoids, the mechanism through which they influence disease is of considerable interest to the physician. It is commonplace by now to say that they do not attack pathogens directly. Clinical observations led to the assumption that they might provide some "protective shield" around the tissues of the body, a barrier quite impermeable to many pathogens. This hypothesis would be consonant with the great nonspecificity of their protective effects, but it is hardly in keeping with the well-known fact that cortisone actually diminishes resistance to some aggressors (e. g., certain pathogenic micro-organisms). The purpose of this communication is to report on recent experiments that suggest an alternative interpretation that is compatible with the fact that these hormones can both protect and sensitize to various nonspecifically injurious agents (noxae). As soon as the principal outlines of the general adaptation syndrome had been recognized, it