Neuropeptide Y (NPY) is a peptide hormone that is expressed, stored, and released in sympathetic neurones together with noradrenaline. Elevated plasma concentrations of NPY have been reported in patients with neural crest tumors (neuroblastoma, pheochromocytoma) and following exercise. We studied plasma concentrations of NPY in children and adults with chronic and terminal renal failure and compared them with those in healthy controls. Neuropeptide Y was significantly higher in children and adolescents receiving peritoneal dialysis (5.3 ± 2.8 pmol/L; n = 11 [mean ± sd]) or hemodialysis (5.4 ± 2.1 pmol/L; n = 14) than in healthy children (2.3 ± 0.9 pmol/L; n = 19) or pediatric patients with impaired renal function who are not receiving dialysis (2.7 ± 0.6 pmol/ L; n = 8; mean glomerular filtration rate, 41 mL/min × 1.73 m²). There was a small but insignificant negative correlation between glomerular filtration rate and NPY concentrations in children with impaired renal function (r = −0.49; P = 0.25). In healthy adults, NPY concentration was similar to that in healthy children (1.8 ± 1.0 pmol/ L; n = 13), and it was significantly elevated in adults receiving hemodialysis (5.9 ± 1.7 pmol/L; n = 16). No significant changes in NPY concentrations were found before and after hemodialysis in pediatric or adult patients. We conclude that plasma concentrations of NPY are elevated in patients with chronic renal failure who are receiving either peritoneal or hemodialysis, but not in patients with moderately impaired renal function. Whether elevated NPY concentration indicates increased sympathetic activity or is caused by reduced NPY clearance remains to be shown.