1. In decerebrated rabbits, repetitive stimulation of the high-threshold afferents of the left common peroneal (CP) nerve evokes prolonged depression of the sural-gastrocnemius medialis (GM) reflex recorded in the same limb. This inhibition is antagonized by co-administration of the opioid antagonist naloxone with the alpha 2-adrenoceptor antagonist idazoxan. The present study was designed to investigate whether such inhibition could be elicited from the contralateral hindlimb or the forelimbs. 2. The sural-GM reflex of decerebrated rabbits was depressed for more than 15 min after stimulation of either ipsilateral or contralateral common peroneal (CP) or median nerves with 500 pulses of 20 V, 1 ms given at 5 Hz. The order of efficacy for generating this inhibition was ipsilateral CP greater than contralateral CP greater than or equal to ipsilateral median = contralateral median. In three of thirty-nine rabbits, stimulation of the median nerves caused facilitation of the sural-GM reflex. 3. Idazoxan (1-2 mg/kg I.V.) did not significantly alter the depressant effect of ipsilateral CP stimulation but reduced that evoked by either median nerve and almost abolished the inhibition evoked from the contralateral CP nerve. 4. Naloxone (0.25 mg/kg I.V.) reduced the effects of ipsilateral CP stimulation, did not alter the inhibition evoked from contralateral CP, and had equivocal actions on the responses to median nerve stimulation. 5. When given together, the two antagonists almost abolished the effects of stimulating the median nerves and the contralateral CP nerve, and markedly reduced the inhibition evoked from the ipsilateral CP nerve. 6. These data show that prolonged inhibition of the sural-GM reflex can be evoked by stimulation of nerves in all four limbs and that in each case the inhibition can be blocked or reduced by co-administration of antagonists to opioid and alpha 2-adrenergic receptors. Such persistent inhibition of reflexes may serve to inhibit withdrawal reflexes in situations where interruptions to normal movement would be disadvantageous.