The analgesic effect of morphine was antagonized in mice pretreated with ginseng total saponin intraperitoneally, intracerebrally and intrathecally. The antagonized effects of morphine analgesia were reversed predominantly by treatment with L-3, 4-dihydroxyphenylalanine in the tail pinch test and 5-hydroxytryptophan in the tail flick test respectively. These indicate that the antagonistic action of ginseng total saponin might be due to their inhibitions of the activation of descending ihibitory systems at the cerebral site as well as spinal. In addition, any appreciable changes of brain biogenic monoamine levels were not observed in mice pretreated with ginseng total saponin at various time intervals. These results obtained suggest that a newly equilibrated state of neurologic function could be found in mice pretreated with ginseng total saponin, and modification of neurologic function in the mechanism for the antagonism of morphine analgesia by ginseng total saponin was more important than the changes of brain biogenic monoamine levels.