Wild-type mice and mice lacking nitric oxide synthase (NOS) of neuronal type or TNF-alpha were subjected to an extradural compression of the thoracic spinal cord, The functional outcome of the hind limbs was assessed by using a motor function score (MFS), The injury resulted in paraplegia of the hind limbs in wild-type mice at day 1 after injury, Gradual recovery was observed during the following 14 days. Injured NOS -/- animals had an improved hind limb motor function during the entire observation period compared to wild-type controls, The difference was statistically significant on day 10 (p < 0.022) and day 14 (p < 0.048) after injury, At the site of injury, there was a trend of gray matter preservation in NOS -/- mice, as measured by MAP2 staining (p < 0.077), Injured mice lacking TNF-<alpha> had the lowest motor score among all the groups on day 1, During the following period, they had motor scores similar to those of wild-type controls and there was no significant difference at any time point. TNF-alpha -/- animals showed a trend of decreased white matter preservation compared to wild-type animals (p < 0.097), Our study shows that after spinal cord injury, mice lacking NOS have a better functional ability of their hind limbs than controls with the same degree of injury. This would indicate that the functional outcome is influenced in a negative way in wild mice by the presence of NO, The degree of secondary damage to the spinal cord might be attenuated in NOS-deficient mice.