Corticotropin-releasing hormone (CRH) exhibits anti-inflammatory properties independent of its effect on adrenal function. We investigated the safety and effect of CRH in nocturnal asthma, a disease where inflammation is prominent. Five subjects underwent an overnight infusion of placebo on the first night, CRH at a 2.5 micrograms/kg/hr on the second night, and three subjects received CRH at 4.0 micrograms/kg/hr on the third night. A significant improvement occurred in overnight change in forced expiratory volume 1 sec. % (delta FEV1) with CRH (+17.4 +/- 9.1%) as opposed to placebo (-25.9 +/- 7.1%), p = 0.024, CRH was well tolerated. Further research with CRH may clarify the pathophysiology of nocturnal asthma.