We investigated the effect of peripheral administration of a selective cannabinoid CB 1 receptor agonist arachidonyl-2-choroethylamide (ACEA), on evoked responses of primary afferents in vivo. Extracellular recordings were made from filaments of the saphenous nerve that responded to noxious mechanical stimulation of their receptive fields and effects of ACEA (30 and 50 μg/100 μl, i.a.) were studied. ACEA significantly inhibited evoked responses, effects that were blocked by co-administration of the cannabinoid CB 1 receptor antagonist AM251 (30 μg/100 μl). These results demonstrate a cannabinoid CB 1 receptor-mediated inhibition of primary afferent nociceptor excitability and provide further support for a peripheral site of action of cannabinoids.