After icv administration, the analgesic action of Hyp was found on the tail-flick and hot-plate tests. The analgesic action potency of icv Hyp was approximately equal to 1 ~20 of morphine and was about 100 times as potent as sc administration. No effect was seen on the analgesic action of Hyp after ip naloxone, the analgesic action of Hyp was no concern of L-enkephalin contents in discrete regions of rat brain either. But icv EGTA markedly enhanced while icv CaCl2 antagonized the analgesic action of Hyp. It was also found that calcium ion content in mice brain markedly reduced when the analgesic action of Hyp appeared. These results suggest that Hyp have significant central analgesic action and the central analgesic action of Hyp may relate to reducing of calcium ion in brain.