IN VERTEBRATES, four major systems of intercellular communication exist: the neural, the endocrine, the neuroendocrine, and the immune system. For many years evidence has accumulated linking the neural, the endocrine, and the neuroendocrine systems, but the immune system was often viewed as essentially autonomous. The enormous recent increase in our knowledge of how the immune system is regulated has led many scientists to postulate that this autonomy may be more apparent than real: that the immune system is subject to endocrine and neural control, and that it exerts, in turn, a reciprocal effect on neuroendocrine systems. In this review we intend to examine the interactions between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis. In the first part of the review we will discuss products and components from the immune system that stimulate or inhibit the HPA axis. These include monokines and lymphokines, i.e. the regulatory secretions of the immune system, and other peptides such as ACTH and β-endorphin, more frequently associated with endocrine tissues but which may also be produced by immunologically reactive cells. In the second part we will examine the reciprocal arm of this relationship, i.e. the products of the pituitary and adrenal gland that can stimulate or inhibit the immune system. We will also touch briefly on the possibility that these interactions may be involved in certain autoimmune diseases. Table 1 and Fig. 3 present a brief overview of the major topics covered in this review. The table and the figure are intended to be complementary and should be consulted together.