The 3- and the 6-glucuronides of morphine have been examined in binding studies and in vivo. The 3-glucuronide had poor affinity in all binding studies whereas the 6-glucuronide potently labeled mu, but not delta or kappa receptors with affinities similar to morphine. Microinjections of the 3-glucuronide directly into the periaqueductal gray were without effect. The 6-glucuronide, on the other hand, was up to 20-fold more potent than morphine following microinjections in the same region. High doses of the 6-glucuronide produced profound seizure activity. All 6-glucuronide actions were sensitive to the opiate antagonist naloxone.