Female rats with lesions of the ventromedial hypothalamus (VMH) were ovariectomized during the static obese stage after body weight levels had stabilized. Following ovariectomy, rats with VMH lesions showed smaller increases in food intake and less body weight gain than non-lesioned controls ovariectomized at the same time. Subsequently, the effects of peripheral injections of estradiol benzoate (EB) on feeding and body weight were examined. Ovariectomized rats with VHM lesions were also less responsive to exogenous EB treatment; they lost significantly less weight in response to estrogen than controls. EB caused a somewhat smaller reduction in food intake by the VMH group but this difference was not significant. Considered together the available data on changes in responsiveness to endogenous and exogenous estrogen following VMH lesions suggest a role for VMH estrogen receptors in the regulation of body weight, but these estrogen receptors may not modulate weight by directly altering food intake as previously suggested.