Effects of three feeding-relevant agents on the single-unit activity of the hypothalamic ventromedial nucleus (VMN) were investigated with tissue slice preparations. Changes in ambient glucose concentrations altered the activity of 39% of the 129 VMN neurons recorded. The predominant effect of glucose was facilitation. Norepinephrine (NE) affected all of the 29 glucose-responsive neurons tested, but only some (33/47) of the neurons unresponsive to glucose. Unlike that of glucose, the effects of NE on neuronal activity were distributed across excitatory, inhibitory, or biphasic responses. In vivo estrogen treatment did not affect neuronal responses to glucose, it modulated the type of neuronal responses to NE from glucose-responsive, but not glucose-unresponsive neurons. These results indicate that glucose, NE, and estrogen act on a common, glucose-responsive, population of VMN neurons but, as judged from their effects on neuronal activity, through different cellular mechanisms. Accordingly, glucose-responsive neurons may serve to integrate information mediated by different feeding-relevant agents.