Opiate antagonists, including receptor antagonists and physiologic antagonists, have been shown to produce beneficial effects in a variety of models of CNS injury and in a variety of species. Opiate antagonists improve spinal cord blood flow, electrical conduction of the spinal cord, pathological changes, and motor recovery following traumatic spinal cord injury in cats. TRH appears to be superior to naloxone in this regard, although direct comparisons between receptor-selective opiate receptor antagonists and TRH have not been made. Similarly, opiate antagonists are effective in improving outcome and reducing pathological changes following ischemic spinal cord injury in rabbits. Beneficial effects for opiate receptor antagonists have also been observed after fluid percussion head injury in cats. Effects of opiate antagonists in the treatment of experimental stroke have been more controversial, although the weight of evidence supports a therapeutic effect in various models and species. Following spinal cord injury, best evidence suggests that pathophysiological responses produced by opioids may be mediated by the dynorphin opioid system and/or the kappa opiate receptor. This issue is of considerable importance, since it may lead to the development of more effective and specific forms of therapy. The role of specific opioid systems and specific opiate receptors in traumatic head injury or cerebral ischemia have not been adequately studied and should be the subject of future investigation. A number of controlled clinical studies are now either planned or under way to investigate the potential therapeutic effects of naloxone and TRH in CNS injury. Data from these studies should be available within the next several years.