ENDORPHINS HAVE BEEN implicated in the pathophysiology of spinal cord injury. The effect of naloxone on the sodium- and potassium-activated and magnesium-dependent adenosine-5'-triphosphatase (Na+-K+/Mg+2 ATPase, EC.22.214.171.124.) activity, lipid peroxidation, and early ultrastructural findings were studied in rats at the early stage of spinal cord injury, produced with an aneurysm clip on the T2-T7 segments. The rats were divided into four groups, The 10 rats in Group I, which had no injury and received no medication, were used for determining Na+-K+/Mg+2 ATPase activity, the extent of lipid peroxidation (by measuring the level of thiobarbituric acid-reactive substances as malondialdehyde), and normal ultrastructural findings. On the 15 rats in Group II, without spinal cord injury, only laminectomy was performed to determine the effect of surgery on the biochemical indices and findings. In the 15 rats in Group III, physiological saline was administered intraperitoneally in an amount equivalent to that of the naloxone administered immediately after spinal cord injury. In the 15 rats in Group IV, 0.5 mg of naloxone was administered intraperitoneally as a single dose immediately after injury and again 60 minutes after injury. The Na+-K+/Mg+2 ATPase activity was promptly reduced after spinal cord injury and remained in a lower level than the levels of Groups I and II during 120 minutes after injury. Naloxone treatment, immediately after trauma, attenuated the inactivation of Na+-K+/Mg+2 ATPase. On the other hand, there was a significant difference in the malondialdehyde content between animals in Groups I and III. Naloxone treatment reduced the malondialdehyde content in Group IV. These data suggest the possibility that naloxone contributes to protecting the spinal cord from injury by effecting lipid peroxidation and cell membrane stabilization. The possible effect mechanism of naloxone, which attenuates the inactivation of Na+-K+/Mg+2 ATPase and decreases lipid peroxidation, is discussed.