The role of ketone body on neural activity and energy metabolism in the brain was investigated. Guinea pig hippocampal slices were prepared, and postsynaptic field potentials (PSPs) were recorded in the granular cell layer of the dentate gyrus. ATP and phosphocreatine (CrP) in the tissue slice were measured after 60 and 120 min incubation in standard medium (1) with 10 mM glucose, (2) with 10 mM glucose plus 20 mM D,L-3-hydroxybutyrate (3-OHBA), (3) without glucose, (4) with 20 mM 3-OHBA instead of 10 mM glucose. In (3), both ATP and CrP in the slice decreased to 40-45% of the original level after 120 min. On the other hand, the ATP level was well maintained even 120 min after incubation in (1), (2) and (4), whereas the CrP level decreased to 62% in (4). Further, slices were incubated in (3) and (4) for 30, 60, and 120 min, and the presence of PSP was tested. In (3), the number of slices from which PSPs could be recorded decreased, and after 120 min PSPs were hardly observed. In (4), that number decreased gradually, and only 45% of the slices showed PSPs after 120 min. These results indicate that 3-OHBA can be a substrate to produce high-energy phosphate but cannot maintain the neural activity as glucose does.