The activity of 5-HT-containing neurons in the brain is activated preferentially in association with motor output in cats. This is especially apparent during changes in muscle tone and during responses mediated by central pattern generators; such as chewing, locomotion and respiration. These and other data support the hypothesis that the primary functions of the 5-HT system in the brain are to facilitate motor output and concurrently inhibit sensory information processing. This hypothesis is applicable phylogenetically, from invertebrates to mammals.