Bath application of alpha-melanocyte stimulating hormone (alpha-MSH) to rat hypothalamic slices inhibited the spontaneous firing rate of continuously firing neurons in the ventromedial hypothalamic nucleus or paraventricular nucleus. This inhibitory effect is most likely direct and independent of synaptic transmission. The alpha-MSH-responsive neurons tested did not respond to neuropeptide Y (NPY) application. On the other hand, alpha-MSH did not inhibit the intraburst firing rate of phasic bursting neurons, although these bursting neurons were highly responsive to a serotonin 5HT2a/2b/2c agonist with a change of firing pattern to continuous firing and an increase in firing rate which was reversed by NPY. These results suggest that a change of neuronal firing rate may represent a neural correlate of satiety induced by anorexic agents.