ACTH (40 IU) was administered intravenously over a period of 8 h to 9 healthy volunteers beginning at 8 a.m., 3 p.m., or 11.30 p.m., and to 3 patients with Addison’s disease beginning at 8 a.m. ACTH produced a significantly greater reduction in rapid eye movement (REM) sleep in the normal volunteers than in the patients with Addison’s disease. In addition, ACTH significantly reduced the total sleep time in the volunteers after infusions beginning at 8 a.m. and 3 p.m.; it did not do so when ACTH was infused during sleep. Delta Sleep was also reduced after the 8 a.m. infusion in the volunteers. These results suggest that ACTH affected sleep through its effect on adrenal corticosteroid secretion. Time appears to be an important aspect in the effects that ACTH and adrenocorticosteroids have upon the central nervous system.