The effects of nitrous oxide, halothane, ether, isoflurane, thiopental, and thiamylal on the excitatory as well as inhibitory responses of single neurons in the midbrain reticular formation (MRF), believed to be one of the most important sites for the regulation of wakefulness, were studied by long-term, extracellular microelectrode recording in cats and rats. All anesthetics except nitrous oxide suppressed the excitatory responses of MRF neurons evoked by somatosensory stimulation. The inhibitory responses markedly were potentiated by both barbiturates but variously affected by other inhalation anesthetics. Blockade of the inhibitory responses (disinhibition) was observed more frequently with the inhalation agents during the light state of anesthesia. Thus, suppression of excitatory responses is likely to be a general feature of the anesthetic state in terms of the behavior of MRF neurons. Further, potentiation of the inhibitory responses might be characteristic of harbiturate anesthesia.