The incorporation of [ 3H]lysine into the trichloracetic acid (TCA) precipitable protein and soluble fractions of brain and spinal cord of rats subjected to immediate transection distal and crush proximal or transection distal, two week interval, and crush proximal of the left sciatic nerve has been studied at 5, 11, and 18 days postoperative. In addition, the regeneration of the nerve fibers was measured. A greater rate of ( P < 0.05) nerve regeneration was noted 11 and 18 days after interval sciatic nerve lesion compared to the simultaneous lesion. In the amino acid uptake studies, the overall trend of [ 3H]lysine into protein in brain and spinal cord showed a peak uptake occurring at 11 days for both simultaneous (S) and interval sciatic lesioned animals, although the effect was most pronounced after interval sciatic lesion. The 11-day interval lesioned group showed the highest uptake of amino acid precursor into protein of all groups averaged over all samples. After interval sciatic lesions, the uptake of amino acid into protein showed the relationship, 11 day group > 18 day group > 5 day group. However, no significant differences in uptake into protein in spinal cord and brain were seen between the simultaneous lesion sciatic animals over postoperative days. In brain, differences between the [ 3H]lysine incorporation into protein of the left (L) and right (R) cortical hemispheres was noted. The incorporation into somatomotor cortex showed a L > R difference which was most pronounced after simultaneous sciatic nerve lesion. Interestingly, the largest R > L difference was in occipital cortex after interval lesions of sciatic nerve. In spinal cord, the protein radioactivity of the L5–6 and S1–4 segments which include most of the affected neurons was greater on the right (unlesioned) side than on the left (sciatic crush) side over all lesioned animals. This effect was most pronounced after interval sciatic lesion. The alteration of central nervous system incorporation of lysine after peripheral nerve (sciatic) lesion and regeneration are discussed.