Summary The effects of hypothalamic stimulation and lesions were studied in alloxan diabetic rabbits. Electrical stimulation of the anterior hypothalamic area increased the severity of diabetes, by further elevation of blood glucose, whereas electrolytic lesions in this area in some animals, produced a marked increase in the response to insulin. Stimulation of the preoptic, supraoptic, posterior and mammillary areas of the hypothalamus did not alter blood glucose levels. The response to insulin in diabetics with posterior hypothalamic lesions was not different from diabetics without lesions. Insulin sensitivity was compared in normal and adrenal demedullated rabbits and no difference was noted. The results indicate that the anterior hypothalamus in the rabbit plays a part in the regulation of blood glucose which is independent of the sympathetico-adrenal system; it more likely involves an alteration of one or more anterior pituitary secretions of ‘diabetogenic’ hormones.