In man, heterotopic painful thermal conditioning stimuli induce parallel decreases in the spinal nociceptive flexion (RIII) reflex and the concurrent sensation of pain elicited by electrical stimulation of the sural nerve at the ankle. Such phenomena may be related to the diffuse noxious inhibitory controls (DNIC) which were initially described in the rat and subsequently documented in humans. In nine subjects in the present study, a 2-min application of a moderately noxious temperature (46 degrees C) to the contralateral hand strongly depressed the RIII reflex elicited in the biceps femoris muscle by electrical stimulation of the sural nerve at 1.2 times the reflex threshold. These depressive effects were maximal during the 2nd min of the conditioning period, showing an almost complete inhibition of the RIII reflex which gradually recovered its baseline value 6-9 min after the end of the conditioning period. Using a double-blind, cross-over design, it was found that these inhibitory effects were completely blocked 5 min after naloxone hydrochloride administration (0.4 mg i.v.) whereas the administration of saline was totally ineffective. The lifting of the inhibitions was compatible with the short duration of the pharmacological effects of naloxone in that the inhibitions were observed again 50 min after the naloxone injection. During all the experimental sessions, heart and respiratory rates remained stable at their control levels. It is concluded that the loop subserving DNIC which ascends from--and redescends to--the spinal cord involves an opioidergic link in man as in experimental animals. Possible implications for hypoalgesia based on the principles of counter-irritation or elicited by naloxone are discussed.