1. It has previously been shown that, in normal humans, heterotopic painful thermal conditioning stimuli induce parallel increase in the thresholds of a spinal nociceptive flexion reflex (RIII reflex) and the concurrent sensation of pain elicited by electrical stimulation of the sural nerve. On the basis of analogous animal studies, we proposed that such phenomena could be related to diffuse noxious inhibitory controls (DNIC), which have been described in the rat. The present study, which was carried out on normal volunteer subjects, was particularly concerned with the extent and temporal characteristics of the depressive effects of DNIC triggered by painful thermal stimuli on RIII reflex activity. In addition, because it was possible that these depressive effects could have resulted from a direct postsynaptic inhibition of motoneurons, a second part of the study was aimed at determining whether or not the heterotopic noxious thermal stimuli also affected the excitability of alpha-motoneurons, as monitored by the monosynaptic Hoffmann reflex (H reflex) technique. 2. In the 11 subjects under study, application of moderate, nonnoxious temperatures (40-44 degree C) to the contralateral hand (via a thermoregulated and agitated waterbath) did not modify the RIII reflex nor the associated sensation of pain. By contrast noxious temperatures clearly depressed the RIII reflex and the concurrent sensation of pain, both during and after the conditioning procedure (CP), in a direct linear relationship to the temperature of the waterbath in the 45-47 degree C range; the maximal depressive effect was observed with the highest conditioning temperature. A significant relationship was also found between the extent of the RIII depression during the CP and that during a 10-min period of post-CP observation. 3. The depressive effects observed on both the RIII reflex and pain were not associated with clear change in autonomic functions. Respiration remained stable during the sessions, with no significant relationship between the temperatures of the waterbath and respiratory rate. Heart rate was slightly but significantly increased during the immersion of the hand in the 46 or 47 degree C waterbaths; this increase, however, ceased with the end of CP. 4. Application of thermal conditioning stimuli produced a slight but nonsignificant increase of the monosynaptic H reflex during the first minute of CP, no matter what was the temperature of the waterbath. However, there were no subsequent variations during the 6-min period of post-CP observation.(ABSTRACT TRUNCATED AT 400 WORDS)