To study possible antinociceptive effects of perineurally administered opioids, the rat infraorbital nerve block (IONB) model was employed for investigations of opioids (morphine, meperidine, buprenorphine, etylketocyclazocine, and fentanyl) of differing receptor selectivity and physicochemical properties such as lipid solubility. Only meperidine in doses >1 mg/kg produced localized analgesia, the duration of which increased dose-dependently. Naloxone failed to counteract the analgesic effects of meperidine. It is concluded that meperidine exerted its effect by a local anesthetic action and not by the activation of opioid receptors in the peripheral nerve. The local anesthetic potency of meperidine was compared with that of lidocaine in peripheral nerve blocks (IONB in rats and sciatic nerve block in guinea pigs), in central nerve blocks (epidural anesthesia in guinea pigs and spinal anesthesia in mice), and in infiltration anesthesia in guinea pigs. Time to onset of block was generally longer for meperidine. Equal amounts of the drugs produced motor blocks of similar durations except in epidural anesthesia where meperidine was clearly shorter. Sensory blocks were longer with meperidine than with lidocaine when applied in equal amounts to the infraorbital nerve and subarachnoidally. The two agents caused a similar duration of sensory block in infiltration anesthesia. Meperidine was shorter than lidocaine in epidural anesthesia. The characteristics of blocks induced by the two agents may be explained by structural differences and associated differences in physicochemical properties such as lipid solubility and pKa.