Cu,Zn superoxide dismutase (Cu,Zn SOD) is one of several anti-oxidant enzymes which defend the cell against damage by oxygen free radicals. Mutations of the SOD1 gene encoding Cu,Zn SOD are found familial amyotrophic lateral sclerosis, a progressive and fatal paralytic disease which is caused by the death of motor neurons in cortex, brainstem and spinal cord. The disease can be reproduced in transgenic mice by expression of mutant human Cu,Zn SOD. Recent studies both in vitro and in vivo suggest that the effect of mutation is to enhance the generation of oxygen radicals by the mutant enzyme. Thus, mutation converts a protective, antioxidant enzyme into a destructive pro-oxidant form which catalyzes free radical damage to which motor neurons are uniquely vulnerable.