Chronic rapid eye movement (paradoxical) sleep deprivation (REM-SD) of rats leads to two conspicuous pathologies: hyperphagia coincident with body weight loss, prompted by elevated metabolism. Our goals were to test the hypotheses that, 1) as a stressor, REM-SD would increase CRH gene expression in the hypothalamus, and that, 2) to account for hyperphagia, hypothalamic gene expression of the orexigen NPY would increase, but expression of the anorexigen POMC would decrease. Enforcement of REM-SD of adult male rats for 20 days with the platform (flowerpot) method led to progressive hyperphagia, increasing to 300% of baseline; body weight steadily declined by 25%. Consistent with changes in food intake patterns, NPY expression rapidly increased in the hypothalamic arcuate nucleus by day 5 of REM-SD, peaking at day 20; by contrast, POMC expression decreased progressively during REM-SD. CRH expression was increased by day 5, both in mRNA and ability to detect neuronal perikaryal staining in PVN with immunocytochemistry, and it remained elevated thereafter with modest declines. Taken together, these data indicate that changes in hypothalamic neuropeptides regulating food intake are altered in a manner consistent with the hyperphagia seen with REM-SD. Changes in CRH, while indicative of REM-SD as a stressor, suggest that the anorexigenic actions of CRH are ineffective (or disabled). Further, changes in NPY and POMC agree with current models of food intake behavior, but they are opposite to their acute effects on peripheral energy metabolism and thermogenesis.