The present study examined the effect of treatment with the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) together with peripheral nerve (PN) graft or brain-derived neurotrophic factor (BDNF) on the survival of CN neurons at the L1 level of the spinal cord following hemisection at T11. In control animals 41% of CN neurons survived 15 days after the hemisection, and 48% of these expressed NOS. Treatment with either PN graft implantation or continuous infusion of BDNF increased the survival rate of CN neurons to 70%; 70% of these expressed NOS. Combined L-NAME and PN graft or L-NAME and BDNF improved the rescue rate up to 94%, but only approximately 33% expressed NOS. Our results suggest that the expression of NOS might adversely influence the neuroprotective function of neurotrophic factors on injured CN neurons in the spinal cord.