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To determine which opioid receptor(s) are involved in local analgesia in the immature animal, agonists specific for \u03bc, \u03ba, and \u03b4 opioid receptors were injected into the intraplantar pad in infant rats and the resultant nociceptive behavior and Fos expression assayed in the formalin test. The \u03ba opioid receptor agonist U50,488 reduced nociceptive behavior in both phases of the formalin test and reduced Fos expression in the dorsal horn of the lumbar spinal cord, at 3 and 21 days of age. Morphiceptin (\u03bc opioid agonist) was analgesic in the 21\u2010day\u2010old pups, but not the 3\u2010day\u2010old pups, measured behaviorally or by Fos expression. DPDPE (\u03b4 opioid agonist) was not analgesic at either age. We also tested the effects of opioid receptor antagonists on morphine's local analgesic action. Naltrexone, and to a lesser extent the \u03bc opioid antagonist CTOP, antagonized morphine's analgesic effect. Kappa and \u03b4 opioid receptor blockers were inactive. The results demonstrate the ability of the \u03ba opioid system to mediate analgesia in the neonate at the site of injury in acute and chronic pain models, that the \u03bc opioid agonists are active later in development, but that morphine is analgesic in part through \u03bc opioid receptors. \u00a9 2003 Wiley Periodicals, Inc. 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