In behaving animals, the activity of brain serotonergic neurons is closely tied to the sleep-wake-arousal cycle: highest firing rate during active waking or arousal; intermediate level of discharge during quiescent states and slow wave sleep; and virtual silence during rapid-eye-movement sleep. Environmental stressors, such as exposure to white noise or physical restraint, and physiologic stressors, such as induction of a febrile response or hypoglycemia, do not activate these cells above the baseline level observed during active waking. Continuing this line of investigation, we have utilized in vivo brain microdialysis in order to determine whether there could be a dissociation between level of serotonergic neuronal activity and release of serotonin at the nerve terminal. Our data indicate that under a variety of the above conditions, neuronal activity and release are not dissociated. We have recently discovered a group of serotonergic neurons whose activity is strongly linked to various oral-buccal activities, such as feeding, grooming, etc. In general, we propose that the brain serotonergic system exerts a modulatory influence over its target structures so as to coordinate their activity with the organism's sleep-wake-arousal state (level of behavioral arousal).