Morphometric studies by histological and teased-fiber methods on myelinated fibers of the C6 and C8 ventral roots were made in cases of myotrophic lateral sclerosis (ALS) and in age-matched controls. In 11 controls myelinated fibers were divided into two groups: large and small fibers. The fiber density was calculated and the actual number of fibers was counted in both groups. The number of large fibers was significantly decreased in 14 of 17 cases with ALS, and correlated with the muscle strength of the ipsilateral upper limb as determined by manual muscle testing before death. The absolute number of small fibers of the C6 ventral root was increased in 3 of 5 cases of ALS. In these cases, there was a group of small myelinated fibers showing very thin myelin lamellae compared to axon circumference, and these were considered as regenerating myelinated fibers. On teased-fiber study, the frequency of fibers with axonal degeneration was 23.8% in ALS in contrast to 0.6% in controls (P less than 0.001). In addition, 5.5% of fibers showed segmental demyelination, and remyelination after segmental demyelination was found in 16.4% of fibers in ALS. These figures were also significantly larger (P less than 0.01) than controls (2.4% and 10.1%, respectively). These results suggest that the essential pathological change in the ventral spinal root in ALS is axonal degeneration of large myelinated fibers, and that Schwann cell involvement may also occur.