Fourth ventricular alloxan injections impair the feeding response to systemically induced glucoprivation. However, the effect of alloxan on responses to centrally administered glucoprivic agents has not been assessed. Therefore, rats implanted with fourth ventricular cannulas were tested for feeding and glycemic responses to centrally administered 5-thioglucose (5TG, 120 micrograms/5 microliter) and subcutaneously administered 2-deoxy-D-glucose (2DG, 250 mg/kg, IP). Subsequently, alloxan (200 micrograms in 5 microliter), alloxan plus 3 M D-glucose, or the saline vehicle solution was injected into the fourth ventricle and the animals were then retested with systemic 2DG and intraventricular 5TG. Feeding responses to both centrally and systemically induced glucoprivic challenge were greatly impaired by alloxan treatment. Thus, feeding elicited by both centrally and systemically induced glucoprivation appears to be mediated by the same central neural substrate. The possibility that the alloxan-damaged cells are glucoreceptors is discussed. In contrast to glucoprivic feeding, the hyperglycemic response to glucoprivation was not impaired by alloxan. Therefore, the neural elements controlling this response may differ biochemically from those controlling feeding.