The Edinger-Westphal nucleus (EW) produces several neuropeptides, including urocortin 1 and cocaine-amphetamine-regulated transcript, which regulate feeding, energy balance, and anxiety. Additionally, the EW projects to feeding and anxiety-regulatory brain areas. The authors tested the effect of lesions of the EW on the consumption of food, water and flavored solutions, metabolic indices, and exploratory behavior on the elevated plus maze in male C57BL/6J mice. EW lesion significantly reduced basal and deprivation-induced food and fluid consumption compared with sham and placement controls, but it did not alter behavior on the elevated plus maze. EW lesion had no effect on indices of basal metabolic activity, including plasma glucose level and body temperature. These effects suggest that the peptidergic neurons of the EW regulate food consumption.