Abstract The response characteristics of single cells in the main sensory trigeminal nucleus were studied in cats anesthetized with chloralose or Nembutal. Peripheral receptive fields in the oro-facial region were located with natural stimuli, stimulated electrically, and the cellular responses interacted with peripheral input (flash or click) and central input (cerebral cortex and thalamic stimulation). Precise location of electrodes was determined histologically with a dye-marking technique. All cells studied had restricted excitatory fields and were activated by hair movement, light touch, or pressure. The responses of fifty per cent of the cells were modified by cortical stimulation (somatosensory areas I and II); corticofugal inhibitory effects predominated and were maximal at 40–80 msec with a duration of 100–300 msec. Thirty per cent of the cells located in the main sensory nucleus exhibited excitatory or inhibitory responses, or both, to flash or click. There was a nonuniform intranuclear distribution of functional cell types; those cells located medially responded to visual and auditory stimuli while cells responding only to oro-facial stimulation were located mainly in the lateral part of the nucleus. The data indicate that considerable modification of somatosensory input occurs at this first central relay nucleus in the trigeminal system.