Seventeen male Wistar albino rats were studied in terms of food intake, food spillage habits, production of feces, and body-weight regulation both before and after a unilateral microinjection of either 6-hydroxydopamine (6-OHDA) or its vehicle (isotonic saline containing.1 mg/ml ascorbic acid) into the medial forebrain bundle (MFB). Eight subjects which sustained a total or near- total depletion of striatal dopamine on the injected side displayed drastically reduced food intake and a steady loss of weight for 3 days after surgery, and throughout the study remained underweight, ingested less food than the controls, and spilled more food per unit amount attempted. Three subjects which sustained between 30% and 64% loss of ipsilateral striatal dopamine, as well as six vehicle-treated controls, showed no sustained loss of weight or reduction of food intake. In addition to ipsilateral striatal dopamine loss, however, marked and consistent reductions of ipsilateral striatal norepinephrine and mesolimbic dopamine were observed in the experimental subjects. All subjects lost weight substantially following 24 h of food deprivation and displayed increased food intake when food was restored, but the lesioned group still ingested significantly less than the control group. It is suggested that a mechanism by which unilateral 6-OHDA-induced damage of the MFB produces a sustained deficit in food intake may be the reduction of the animal’s body-weight set point.