Human peripheral leukocytes1,2 infected by virus or treated with endotoxin will, like unstimulated mouse spleen macrophages3, synthesize immunoreactive corticotrophin (ir-ACTH) and endorphins. The ir-ACTH produced appears to be identical with authentic ACTH1-6, while enough of the material has been produced in hypophysectomized mice infected with virus to demonstrate a steroidogenic reponse6. Because the production of ACTH by in vivo pituitary cells and by leukocytes is suppressed by dexamethasone both in vitro7 and in vitro6, suggesting8 that the production of ACTH and endorphins by leukocytes is indeed controlled, we have investigated the effects of corticotropin releas-ing-f actor (CRF), which is known9 to regulate the pituitary production of both ACTH and β-endorphin. We now report that the production of ACTH and endorphins by leukocytes is indeed induced by synthetic CRF10 and, in turn, suppressed by dexamethasone, suggesting that, as in pituitary cells, the pro-opiomelanocortin (POMC) gene may be expressed and similarly controlled in leukocytes. © 1986 Nature Publishing Group.