Orexin-A and orexin-B are newly discovered neuropeptides which are implicated in feeding behavior and arousal state. We studied immunoreactive(IR)-orexin-A concentrations in human plasma by radioimmunoassay. IR-orexin-A concentrations in plasma obtained from 17 healthy subjects in the morning were 1.94 +/- 0.24 pmol/liter (mean +/- SEM). IR-orexin-A levels in the plasma obtained at night were not significantly different from those obtained in the morning in 9 female subjects. The HPLC analysis of the plasma extract showed two immunoreactive peaks; one peak eluting in an identical position to synthetic orexin-A, and one eluting earlier. This study has shown for the first time the presence of orexin-A in human plasma.