The first studies related to the analgesic effects induced by electrical stimulation of the periaqueductal and periventricular structures in the rat 12 and the cat 15 have implicated the possible participation of serotonergic mechanisms in this kind of analgesia 1, 2, 5, 6. More recently, in the cat, extensive mapping at the level of the brain stem has clearly pointed out the role of serotoninergic structures corresponding to several raphe nuclei (dorsalis, centralis superior, centralis inferior) 15, 17, 1s. In these studies it has been reported that analgesic effects can be achieved when repeated, short (< 1 min) periods of central stimulation are delivered. However, at the time this work was performed, we did not consider that the efficacy of stimulation might vary after the application of prolonged periods of repeated stimulation. Since'tolerance'to periaqueductal gray matter (PGM) stimulation has already been described in the raO and man 9, the purpose of the experiments described in this report was to determine whether it would be possible to observe this phenomenon of tolerance development in the cat by prolonged stimulation of raphe nuclei. Taking into account the probable involvement of serotonergic mechanisms in electrical analgesia, our second objective was to see whether the eventual decrease of analgesia following the application of long periods of central stimulation was affected by the administration of a serotonin precursor, 5-hydroxytryptophan (5-HTP). Analgesia was tested by applying pinches to the tail and the 4 limbs 15, but when precise measurements of the time course of the phenomenon were required we determined the effects of central stimulation on the threshold of the jaw opening reflex (JOR) induced by tooth pulp stimulation 19.