Neuropeptide Y (NPY) is demonstrated to be involved in the pathophysiology of Alzheimer's disease, as well as somatostatin. We measured the plasma NPY content in patients with Alzheimer's disease and healthy control subjects (n = 25) by HPLC coupled with radioimmunoassay. The difference in screening pattern of NPY-like immunoreactivity in 50 fractions eluted by HPLC obtained from the plasma peptide-rich fraction between patients with Alzheimer's disease and healthy controls suggested the abnormal metabolism of plasma NPY in patients with Alzheimer's disease. Plasma NPY in patients with Alzheimer's disease was significantly decreased compared with that in healthy controls, which was compatible with the findings obtained from the brain and cerebrospinal fluid and could be involved in the pathogenesis or pathophysiology of Alzheimer's disease.