Cells of the immune system can be stimulated to secrete POMC-derived peptides such as beta-endorphin and ACTH. Recently, it has been reported that CRF induces beta-endorphin secretion by human peripheral blood mononuclear cells in vitro (1). It has been shown that interleukin-1 (IL-1) mediates the CRF-induced secretion of beta-endorphin by lymphocytes in vitro. In the present report it is demonstrated that sc administration of CRF to rats can also induced beta-endorphin secretion by lymphocytes from spleen and mesenteric lymph nodes. Moreover, this CRF-induced secretion of beta-endorphin coincides with enhanced secretion of IL-1 by macrophages. Previously, we reported that IL-1 can activate CRF neurons in the hypothalamus of the brain. Our data indicate the existence of an intricate relationship between CRF and IL-1, peptides that can be viewed as playing a pivotal role in the interaction between the central nervous system and the immune system.