This review summarizes the evidence available on the involvement in stress of different classes of benzodiazepine receptors and their putative endogenous ligand, diazepam binding inhibitor (DBI), with particular reference to their role in modifications of the immune response. The presented data from in vitro, experimental, and clinical studies suggest that benzodiazepine receptors and DBI play a major role in regulating steroid production in both the adrenals and central nervous system, and may be involved in the activation of the hypothalamic-pituitary-adrenal axis in stress response.