We studied a family in which three siblings had an identical clinical feature indistinguishable from familial amyotrophic lateral sclerosis (ALS), consisting of progressive generalized neurogenic muscular atrophy with hyporeflexia and normal sensations beginning in the fourth decade. The duration of illness was about 4 years in all affected members. Autopsy of one patient revealed multiple foci of spongy degeneration in the white matter of the spinal cord, brain stem, cerebellum, and the thalamus, characterized by vacuoles of various size, foamy macrophages and degenerating swollen axons. These changes were most marked in the spinal cord, where there was neither pyramidal tract involvement nor neuronal loss in the anterior horn. The pathological findings were different from those of ALS. A similar disease affected the siblings' mother, suggesting an autosomal dominant inheritance. The disease in the kindred, therefore, appears to be a unique hereditary disorder.