The present study was performed to explore the possible involvement of the arcuate nucleus of hypothalamus (ARH) and beta-endorphinergic pathway in the connection from nucleus accumbens to periaqueductal grey (PAG). It was found that the analgesic effect of morphine administered to nucleus accumbens of the rabbit was significantly attenuated by the antiserum against beta-endorphin (beta-EP) injected into PAG. The antagonistic effect was totally abolished by lesioning of the ARH. However, in the rabbit with ARH lesioning, no significant change in basal nociceptive threshold was seen nor was there any significant change in the efficacy of analgesia induced by injecting morphine into nucleus accumbens. The latter effect was attenuated by intra-PAG-administered naloxone, as in the normal control rabbits. These results indicate that (1) ARH and its efferent beta-endorphinergic fibers are involved in the descending pathway from the nucleus accumbens to PAG, subserving an antinociceptive effect, (2) endogenous opioid peptides other than beta-EP seem to play an equally important role in mediating analgesia.