To study anorexia in chronic renal failure patients (CRF), we measured appetite-related hormones in 7 CRF patients and 4 controls. Plasma concentrations and fractional changes from baseline (values from Day 1, 08 hour) are listed as control versus CRF (means±SEM). Leptin, ng/ml, though higher in CRF, 5.6 ± 1.7 and 34 ± 17, was suppressed after fasting; decrements were -51 ± 9 % and -55 ± 8 %. Nocturnal surge present during feeding was abolished upon fasting in both groups. Neuropeptide Y (NPY, pg/ml) was elevated in CRF, 72 ± 12 versus 304 ± 28 (p=0.0002). NPY rhythm, reciprocal to that of leptin, was muted in CRF. Basal cortisol, ug/dl, was similar in both groups, 17 ± 3 and 17 ± 2. In the controls, cortisol peaked in the morning and declined in the evening. CRF showed blunted cortisol suppression. Decrements were -61 ± 3% and -20 ± 9% at 18 hour, Day 1 (p = 0.008), -61 ± 8% and -26 ± 8% at 20 hour, Day 2 (p = 0.02). Basal ACTH, pg/ml, 25 ± 5 and 54 ± 16, as well as diurnal pattern, were not statistically different between the groups. Baseline insulin, uU/ml, was 6 ± 1 and 20 ± 9. During fasting, insulin was suppressed, respectively, to -64 ± 10% and -51 ± 9%. Upon refeeding, increments were 277 ± 96% and 397 ± 75%. Thus, in our CRF patients, anorexia was not due to excess leptin or deficient NPY. Impaired cortisol suppression should favor eating. Insulin suppression during fasting and secretion after feeding should enhance both eating and anabolism. The constant high NPY suggests increased tonic hyper secretion.