Both acute and chronic effects of lysergic acid diethylamide (LSD) and 5-methoxy-N, N-dimethyltryptamine (5-MeODMT) on the dorsal root potential (DRP), evoked by stimulation of the nucleus raphe magnus of the cat, were examined. Single injections of LSD potentiated while those of 5-MeODMT inhibited the raphe-evoked DRP. The electrophysiologic response produced by each drug correlates well in dosage and time-course with their reported behavioral effects. Following four consecutive daily injections of LSD, complete tolerance developed to the potentiating effect of LSD on this potential. A similar pretreatment schedule with 5-MeODMT failed to alter its acute inhibitory effect on the DRP. These results correlate well with the development of tolerance to the behavioral effects of LSD and 5-MeODMT. This system may thus provide a unique electrophysiological model to examine the effects of these drugs.