Study design: In order to study the role of gender in recovery, we induced a thoracic compression spinal cord injury (SCI) separately in 2-month-old male and female C57Bl/6 mice. Objectives: We intended to assess effects of gender on recovery of hindlimb motor function and to correlate these with histomorphologic profiles of injured spinal cord tissue. Methods: Locomotor function was evaluated by three means: a modified locomotor scoring system for rodents, beam walking and computerized activity meter. Histology was analyzed by comparison of hematoxylin and eosin-stained perfused specimens. Results: Locomotor scores were 2.270.9 on day 1 in male mice, while, in contrast, they were significantly higher, 7.371.7, in females (Po0.02). On day 14 Basso, Beattie and Bresnahan scores were 9.572.2 in male mice and 16.072.2 in females (Po0.03). Terminal histology showed that the spinal cord architecture was relatively better preserved in female mice and that the extent of necrosis and infiltration of inflammatory cells was less compared to males. Setting: Neurobiology Research Laboratory of University of Kansas Medical School in US Department of Veterans Affairs Medical Center, Kansas City, Missouri. Conclusion: We found that the severity of the initial injury as well as the ultimate recovery of motor function after SCI is significantly influenced by gender, being remarkably better in females. The mechanism(s) of neuroprotection in females, although not yet elucidated, may be associated with the effects of estrogen on pathophysiological processes (blood flow, leukocyte migration inhibition, antioxidant properties, and inhibition of apoptosis).