The primary objective of this study was to investigate the effects of topical L-arginine and Ng-nitro-L-arginine methyl ester vs the role of ischemia in contributing to secondary injury after experimental acute spinal cord trauma. Twenty-six rabbits were submitted to spinal cord compression at the T7/8 level. The animals were divided into three groups: no applied drug (n=6), L-arginine (n=10), and Ng-nitro-L-arginine methyl ester (n=10). L-arginine was topically administered at a dose of 10 micromol (1.742 mg) per kg immediately after acute spinal cord injury. Ng-nitro-L-arginine methyl ester was applied topically at a dose of 10 pmol (10 mg/kg) immediately after acute spinal cord injury. Cortical somatosensory evoked potentials were recorded before injury and 1 min, 15 min, 30 min, and 60 min after injury. Physiological parameters were followed before, during, and I h post injury. Light and electron microscopic analysis was performed in all of the groups. In contrast to group 1, the edema of perineural, axoplasm, or surrounding tissue, the thickening of walls of the arterioles and venules, and the degeneration in myelinated axons in groups 2 and 3 were well observed. However, no differences between group 2 and group 3 occurred.