We have explored the activity of brain serotonin (5-hydroxytryptamine; 5-HT) neurons in behaving cats exposed to a wide variety of behavioral and physiological conditions. In general, the activity of these neurons is strongly related to spontaneous changes in behavioral state (being highest in active waking and lowest during REM sleep). Across a wide variety of experimental manipulations, the activity of serotonergic neurons was relatively unchanged. This includes dramatic alterations in general physiology. However, one condition, motor activity, strongly affected neuronal activity. A general relationship obtains between level of tonic motor activity and serotonergic neuronal activity across all major groups of serotonergic neurons. Superimposed upon this in some neurons is an additional relationship where a further, often dramatic, activation is seen in association with repetitive, central pattern generator (CPG)-mediated behaviors. The exact nature of this relationship varies both with the specific serotonergic neuronal group and within a particular group. We hypothesize that the primary function of this increased serotonergic neuronal activity is to facilitate behavioral output by coordinating autonomic and neuroendocrine function in association with motor demand, and by a concomitant general suppression of afferent input from sensory processing channels.