The brain-gut peptide neuromedin U (NMU) has been identified recently as a physiological regulator of food intake. To further investigate the central role of NMU in energy homeostasis, we examined the distribution of NMU transcript and the effect of intracerebroventricular administration on several physiological parameters and on the pattern of c-Fos activation. Here we report that intracerebroventricular administration of NMU to 24-h fasted rats resulted in a decrease in subsequent food intake and body weight gain. NMU administration activated neurons in several brain regions implicated in the regulation of feeding behavior. Activated cells included catecholaminergic neurons of the arcuate nucleus and brain stem. Distribution studies revealed NMU expression in the caudal brain stem (nucleus of the solitary tract and inferior olive) and pituitary, with significant levels in the pars tuberalis. This contradicts earlier published observations. In obese (fa/fa) Zucker rats, decreases in NMU expression were detected in the nucleus of the solitary tract, pars tuberalis, and pars distalis, whereas in the fasted rat, a decrease in NMU transcript was detected in the pars distalis. These results confirm the effects of NMU on feeding and suggest additional roles for NMU in neuroendocrine function.