We have used the anorexia shown by rats given hypertonic saline to drink to investigate central mechanisms that can inhibit feeding. Rats dehydrated in this manner for 3 or 5 days showed a severe attenuation of the compensatory feeding observed after an overnight fast compared with control euhydrated rats or rats whose food was restricted to match the intake of anorexic rats. Food intake after injections of 2-deoxy-D-glucose (2-DG) was also significantly decreased in dehydrated animals compared with that after a 2-DG injection given before dehydration. However, all the dehydrated animals demonstrated a robust eating response after water was returned whether they had received injection of 2-DG or vehicle. Despite a profound reduction in 2-DG-induced feeding, other glucoregulatory responses to 2-DG remained intact in dehydrated animals. After 2-DG injection, corticosterone secretion and blood glucose were significantly elevated from preinjection values whether or not animals were dehydrated. Thus the mechanisms responsible for anorexia in dehydrated animals specifically target stimulatory feeding pathways but leave intact other counterregulatory glucometabolic motor events.