The relationship between adrenocortical function and immunity is a complex one. In addition to the well-known detrimental effects of large, pharmacologic dosages of glucocorticoids upon the immune process, there is impressive evidence that physiologic amounts of cortisol, the chief glucocorticoid normally produced by the human adrenal cortex, is necessary for the development and maintenance of normal immunity. This evidence is reviewed, and the importance of differentiating between physiologic and pharmacologic dosages and effects is discussed. The popular use of synthetic derivatives of cortisol, which differ greatly from the natural hormone in strength, and the dynamic nature of the normal adrenocortical response, which varies with the degree of stress being experienced, have contributed to the confusion. Further studies of the nature of the beneficial effect of cortisol, and possibly of other normal adrenocortical hormones, upon immunity in humans are needed, especially in view of recent evidence of a feedback relationship between the immune system and the hypothalamic-pituitary-adrenal axis, and with the increasing awareness not only that the immune process provides protection against infection, but also that its impairment seems to be involved in the development of autoimmune disorders, malignancies and the acquired immunodeficiency syndrome (AIDS).