Brain serotonergic neurons display a distinctive slow and regular discharge pattern in behaving animals. This activity gradually declines across the arousal-waking sleep cycle, becoming virtually silent during rapid eye movement sleep. The activity of these neurons, in both the pontine and medullary groups, is generally unresponsive to a variety of physiological challenges or stressors. However, these neurons are activated in association with increased muscle tone/tonic motor activity, especially if the motor activity is in the repetitive or central pattern generator mode. We interpret these data within the following theoretical framework. The primary function of the brain serotonergic system is to facilitate motor output. Concurrently, the system coordinates autonomic and neuroendocrine function with the present motor demand, and inhibits information processing in various sensory pathways. Reciprocally, when the serotonin system is briefly inactivated (e.g., during orientation to salient stimuli), this disfacilitates motor function and disinhibits sensory information processing. It is within this context that serotonin exerts its well-known effects on pain, feeding, memory, mood, etc.