BACKGROUND Orexins A and B are neuropeptides that regulate feeding behavior and are localized exclusively in neurons within and around the lateral hypothalamic area. Intracerebroventricular injection of orexin A stimulates food consumption in rats. Plasma concentrations of orexins may reflect nutritional states and may have clinical significance in patients on hemodialysis. In this study, we investigated the relationship between plasma orexin concentrations and nutritional states in patients on hemodialysis. METHODS We measured plasma orexin concentrations in patients on hemodialysis (HD group, n = 67), patients with IgA nephropathy (n = 10), patients with diabetes mellitus (n = 11) and healthy controls (n = 10). We examined the relationships between plasma orexin concentrations and nutritional indices. RESULTS Plasma orexin A concentrations were significantly higher in the HD group than in the control group and showed a significant correlation with serum creatinine. In all subjects, there was a positive correlation between the plasma orexin A concentration and the serum creatinine concentration, but there were no correlations between these concentrations in each group. In the HD group, plasma orexin A concentrations had a significant positive correlation with the serum albumin concentration and percent creatinine generation rate (%CGR). Multiple regression analysis demonstrated that %CGR was the only independent factor associated with plasma orexin A concentrations. CONCLUSIONS Plasma orexin A concentrations are increased in patients on hemodialysis. It is possible that the kidney plays a major role in the clearance of orexins. The plasma orexin A concentration is significantly correlated with %CGR, and it may be able to be used as a clinical marker of the nutritional state in patients on hemodialysis.