The expression of nitric oxide synthase was studied in human postmortem cervical spinal cord from four individuals with amyotrophic lateral sclerosis (ALS) and four individuals who had died from non-neurological causes. A novel autoradiographic method employing [3H]nitro-L-arginine, a potent inhibitor of the enzyme, as the binding ligand, was used. The expression was quantified in four discrete subregions of the grey matter, and in the dorsal and ventral white matter. The maximum density of binding in the superficial dorsal, deeper dorsal horn, and intermediate subregions of the grey matter was similar in ALS and control tissue, but it was higher in the ALS tissue, in the ventral horn, and in the dorsal and ventral white matter, compared to the corresponding regions in the control tissue. Saturation analysis of the binding indicated a single population of high affinity binding sites in all subregions in the control tissue. However, in the ALS tissue, in all subregions, the presence of two populations of binding sites with different ligand binding affinities were indicated. It is possible therefore that the expression of an inducible isotype of nitric oxide synthase may contribute to the neuropathic changes seen in ALS.