The beneficial effects of naloxone observed in a number of pathophysiological states are based on the premise that there is overactivity of the endor-phin system in such states. As the endorphins increasingly are being implicated in a variety of pathophysiological states, naloxone or similar opioid antagonists are likely to be employed as therapeutic agents to modify the function of endorphins. However, it must be noted that to date most of the results with naloxone in these states are based on animal studies and there is a marked paucity of human clinical data. Due to species differences, experimental results obtained from animal studies are not always applicable to humans. Additionally, the action of naloxone is short in duration. Naltrexone, a longer acting antagonist, or perhaps a more receptor specific endogenous opiate antagonist, if developed, may be of value in shock, spinal cord injury, stroke, respiratory failure and drug overdose. More human studies will be required to confirm the validity of animal experiments performed using naloxone. It is clear that the physiologic roles of the endogenous opiates, other than their analgesic properties, are not fully understood and naloxone or related agents are likely to hold clinical interest in the foreseeable future.