Morphine and nalorphine were shown to have a peripheral analgesic effect on conscious guinea pigs, producing a decrease in the vocalization response to noxious electrical stimulation. Naloxone antagonized the effect of morphine and nalorphine. 2. Locally administered clonidine had a peripheral analgesic effect on conscious guinea pigs, producing a decrease in the vocalization response to noxious electrical stimulation. 3. The peripheral analgesia of clonidine was antagonized by yohimbine and naloxone. The analgesic effect of clonidine was 250-300 times more potent than that of lidocaine. 4. It is suggested that alpha 2-adrenergic receptor agonists may activate enkephalin-like substances released at the peripheral level.