Responses of sleep-related neurons in the preoptic area (POA) to stimulation of the locus coeruleus (LC) and the ventrolateral medulla (VLM), components of the reticular activating system, were recorded in the unanesthetized, head-restrained rat. Single-pulse stimulation of the LC and the VLM, respectively, inhibited 50% and 54% of 30 sleep-active neurons and excited 47% and 67% of 34 waking-active neurons. The remaining neurons were mostly unaffected. Seventy-three neurons that were not related to a sleep-wake state were mostly (i.e., 73-80%) unresponsive to stimulation. The high incidence of responses by sleep-related neurons suggests that neural inputs from the LC and VLM regulate the hypnogenic mechanisms in the POA. Stimulation of the LC antidromically activated 15% of sleep-active neurons and 11% of waking-active neurons. Thus, some of the sleep-related neurons in the POA may regulate LC neurons. In a later stage of the experiment, we used isoflurane-anesthetized rats that had been used for recording sleep-related neurons. Antagonists for adrenoceptors at a concentration of 10 microM were applied to neurons through a multibarrel micropipette to examine the involvement of noradrenaline in the responses as a neurotransmitter. Application of the alpha 2-blocker, yohimbine, attenuated the inhibitory responses in all 7 neurons tested. The beta-blocker, timolol, and the alpha 1-blocker, prazosin, did not alter any of the inhibitory responses. On the other hand, timolol attenuated the excitatory responses in 4 of 7 neurons, and prazosin attenuated the excitatory responses in 5 of 12 neurons. Yohimbine did not affect the excitatory responses. Thus, the LC and the VLM probably inhibit sleep-active neurons through alpha 2-adrenoceptors and excite waking-active neurons through either beta- or alpha 1-adrenoceptors.