Background: Neuropeptide Y (NPY) is a 36-amino-acid peptide that was originally isolated from the porcine brain. NPY, in contrast to leptin, is one of the most potent appetite stimulants. In some previous studies, NPY was found to be correlated with mean blood pressure (MBP) and fluid volume in patients on hemodialysis (HD), contributing to volume-induced hypertension. However, it is still unclear which NPY-sensitive neuronal pathways are responsible for the various changes seen in response to central NPY administration. In this study we analyzed the correlation of circulating levels of NPY with parameters of nutritional conditions, and we investigated the relationships between NPY concentrations and clinical markers of fluid volume in patients on HD. We also evaluated the effects of high-flux dialysis membranes on plasma NPY levels as compared with those of low-flux membrane. Methods: Plasma NPY concentrations in patients on regular HD were measured using commercially available radioimmunoassay (RIA) kits. We examined the relationship between plasma NPY concentration and other clinical indices in patients on HD. Results: Plasma NPY concentrations were inversely correlated with the serum urea nitrogen levels (r = –0.32) as well as protein catabolic rate (PCR) (r = –0.28). Plasma NPY was also correlated with the increase in body weight between HD sessions (r = 0.29). On the other hand, plasma NPY concentrations were not correlated with MBP, atrial natriuretic peptide (ANP), or adrenomedullin (AM). The reduction rate of plasma NPY with a high-flux dialysis membrane was significantly higher than that with a low-flux dialysis membrane. Conclusions: The secretion of NPY may be enhanced in a poor state of nourishment and stress induced by fluid volume overload in patients on HD, and plasma NPY is removed by a high-flux dialyzer.