Central injection of hypocretins/orexins in rats induces water intake. As the subfornical organ (SFO) plays an important role in drinking behavior, hypocretins may excite SFO neurons. In this study, effects of hypocretins on SFO neurons were investigated electrophysiologically in slice preparations. In extracellular recordings, hypocretin-1 excited SFO neurons, but hypocretin-2 did not or it was little. After the block of synaptic inputs, the excitatory responses to hypocretin-1 remained, but some disappeared. In whole-cell patch-clamp recordings, hypocretin-1 reduced the frequencies of miniature inhibitory presynaptic currents with inward currents occasionally in SFO neurons, but hypocretin-2 did not. These results suggest that hypocretin-1 excites SFO neurons via the activation of hcrtR1 on premembranes and postmembranes.