Little information is available regarding the interaction of anesthesia and spinal cord injury. In this study male, Sprague-Dawley rats (n = 140) of similar weights underwent a graded lumbar spinal cord injury by inflation of an epidural balloon, to determine the effect of anesthesia upon the severity of injury. One of three different anesthetic regimens (halothane, fentanyl/nitrous oxide, or spinal lidocaine) were administered during the time of injury, and the neurologic outcome was compared to an awake control group. Physiologic variables (pH, Paco2, Pao2, hematocrit, mean arterial pressure, serum glucose, and temperature) were maintained within normal ranges. Dose-response curves were constructed evaluating the relationship between the duration of balloon inflation versus the percentage of animals with a sustained neurologic deficit. The dose-response curves were analyzed for differences by use of a group t test. The incidence of clinical spinal cord injury (hindlimb paralysis) was lower in all three anesthetic groups as compared to awake controls (P < 0.05). The balloon inflation time required to produce a sustained neurologic deficit in 50% of rats for each group was (minutes [mean ± SD]): 1) awake—10.0 ± 2.3; 2) spinal lidocaine-19.6 ± 11.6, 3) halothane—19.8 ± 6.7; and 4) fentanyl/nitrous oxide—37.9 ± 18.7. This observation demonstrates that, in this model of spinal cord injury, various anesthetics improve neurologic function as compared to the awake state. It does not indicate any one technique as being either more favorable or deleterious in determining the final neurologic outcome. The precise mechanism(s) explaining how anesthetics decrease the incidence of spinal cord injury are likely to be multiple, complex, and as yet not totally understood.