A study has been made of the effect of brain stem lesions upon ponto-geniculo-occipital PGO) wave activity. The results include the following. (1) Midline lesions, in the region of the raphe nuclei, caused a transient increase in waves having the characteristics of PGO REM. After 1–4 days these waves were suppressed during wakefulness but continued to appear during slow wave sleep, as well as during REM sleep. (2) The disturbance in the regulation of PGO REM was greatest in the animals with large lesions, involving several raphe nuclei. (3) Unilateral parasagittal cuts, 1.5 mm lateral to the midline in the region of the raphe nuclei, caused changes in PGO wave activity similar to those following midline lesions of comparable extent. (4) Pentobarbital, administered several days after a raphe lesion, gave rise to a transient increase in PGO wave activity. The recordings resembled those obtained s shortly after the lesion was made. (5) The onset of drug-induced wave activity, following treatment with PCPA, was accelerated in animals with midline lesions of the raphe area. (6) Stimulation of the pacemaker region of the pons, on the side ipsilateral to an extensive parasagittal cut, consistently evoked lateral geniculate responses during slow wave sleep, as well as during REM sleep. Stimulation of the pacemaker on the opposite side of the pons evoked lateral geniculate responses only during REM sleep. These results support the hypothesis that 5-HT containing neurons, having their perikarya in the raphe nuclei, play an important role in the normal their perikarya in the raphe nuclei, play an important role in the normal regulation of PGO REM.