Corticotropin-releasing hormone (CRH) is a neuropeptide thought to play a role in appetite regulation. In this report, we used a serial cerebrospinal fluid (CSF) sampling technique to examine the relationship between CSF CRH, plasma ACTH and cortisol and perceptions of hunger and satiety in fasting and sated volunteers. CSF was withdrawn continuously from 11:00 AM to 5:00 PM via an indwelling subarachnoid catheter. Blood was withdrawn every 10 min via an antecubital vein catheter. Fed subjects received a meal at 1:00 PM. Subjects who were fed had lower post-prandial ratings on hunger scales and higher ratings on satiety scales. Fed subjects also had slightly lower levels of CSF CRH after feeding. Furthermore, fed subjects had higher ACTH and cortisol concentrations in the first 3 h; by the fourth h the opposite was true. Our findings do not support the hypothesis that CNS CRH is a central satiety factor in the human. Instead our findings of slightly diminished CSF CRH levels after feeding may be accounted for by the rises in glucocorticoids and their associated negative feedback effects on CNS CRH. Alternatively, our findings could also reflect changes in CRH levels associated with feeding in multiple brain areas and in the spinal cord with the net effect being in the negative direction.