Adult female rats were adapted to a macronutrient self-selection regimen which allowed them ad libitum access to separate sources of protein, carbohydrate, and fat. The rats were then given either ventromedial hypothalamic (VMH) lesions, paraventricular hypothalamic (PVH) lesions, parasagittal knife cuts through the medial hypothalamus (CUT), or sham lesions and their macronutrient selection was studied for 60 days. Following surgery the VMH, PVH, and CUT rats overate and became obese compared with controls. The hyperphagias of the three groups were similar, although the CUT group gained more weight than did the PVH and VMH groups. All groups overate primarily by increasing their carbohydrate intake. The VMH and CUT groups, in addition, increased their protein intake such that their percent protein intake remain unchanged. The PVH group failed to increase its absolute protein intake and thus decreased its percent protein intake. Except for a transient increase, fat consumption was not affected by the lesions or knife cuts. During the 2nd postoperative mo (static phase) the total caloric intakes and the carbohydrate intakes of the VMH, PVH, and CUT groups returned to near normal levels. Rats with misplaced PVH lesions displayed minimal hyperphagia and failed to outgain controls but yet showed the same altered macronutrient selection pattern as did rats with obesity-inducing PVH lesions. Measurements of resting insulin levels at the end of the experiment revealed hyperinsulinemia in the VMH and CUT groups but normal insulin values in the PVH group. These results demonstrate that VMH lesions, PVH lesions, and medial knife cuts produce similar hyperphagia syndromes associated with carbohydrate-specific overeating, but that they differentially affect protein selection and resting insulin levels.