Although the physiological functions of the endogenous opioid systems are not yet clearly established, it is widely accepted that they exert an inhibitory control on pain transmission. However, the well-documented hypoalgesic effects of low doses of the opiate antagonist naloxone both in animals and humans do not fit in with this concept. The present investigations, at two different spinal/medullary levels (viz. cervicotrigeminal and lumbar) demonstrate that, in the rat, a noxious mechanical stimulus does not alter the release of Met-enkephalin-like material (MELM) from neural segments related to the stimulated area of the body, but does increase its release from other segments. Electrophysiological studies have already demonstrated the existence of such heterosegmental mechanisms, notably 'diffuse noxious inhibitory controls' (DNIC), which are naloxone-reversible and could play an important role in pain perception. The involvement of spinal enkephalins in DNIC would seem to mean that the heterosegmental spinal release of MELM triggered by noxious stimuli participates in pain processes.