To elucidate the anorectic action of the endogenous organic acid, 3-hydroxybutyric acid (3-HBA), its effects on neurons in both the rat ventromedial hypothalamic nucleus (VMH) and the lateral hypothalamic area (LHA) were examined. Iontophoretic application of 3-HBA significantly facilitated the firing rate of VMH neurons, whereas facilitation and inhibition were observed in the LHA. These responses were specific to the glucoreceptor neurons in the VMH and glucose-sensitive neurons in the LHA. Intracellular recordings from brain slice preparations revealed that 3-HBA depolarized the cell membrane of the VMH neuron with an associated increase of membrane input resistance. This was similar to the effect of glucose on glucoreceptor neurons in the VMH. These results suggest that 3-HBA may modulate hypothalamic chemosensitive neuron activity as well as function as an endogenous satiety factor.