The effects of naloxone and thyrotropin releasing hormone (TRH) were compared in an incremental air embolization model of experimental stroke in dogs. Naloxone treatment significantly improved the cortical somatosensory evoked response and had a beneficial effect on local cerebral blood flow, whereas TRH treatment had no effect on these variables. These findings may implicate endorphins in the pathophysiology of stroke and indicate that naloxone may have a therapeutic role in this condition. Moreover, the lack of effect of TRH in this model, in contrast to its therapeutic effect in experimental spinal injury, indicates that the pathophysiologic responses to ischemic cerebral injury and traumatic spinal injury may differ.