AbstractAdrenal gland metabolism is markedly altered in heroin addicts. During day-time hours, the addict may suffer corticoid deficiency of the addisonian type, and in the evening, an excess of the cushingoid type. The high plasma levels of cortisol that are found in the evening in addicts antagonize endogenous opioids in a manner similar to naloxone. In the present study, 72% of the heroin addicts who sought treatment demonstrated reduced adrenal cortisol reserve. Effective immune and stress responses are dependent on adrenal cortisol reserve. This finding provides an explanation for the heroin addict's vulnerability to AIDS and other infectious diseases. One of methadone's greatest attributes is that it helps normalize adrenal metabolism. Clinical methods to at least partially correct adrenal metabolism may enhance current opioid addiction treatment modalities.