This report concerns a comparative immunocytochemical and ultrastructural investigation on pericapillary rosettes (PR) in the lumbar spinal cords of 21 patients with amyotrophic lateral sclerosis (ALS) and 18 age-matched neurologically normal individuals. The purpose of the study was to determine the alteration of PR in relation to the neuronal loss in ALS. The PR were almost always positively immunostained for phosphorylated neurofilament, and some PR immunoreacted with antibodies to synaptophysin and β-amyloid precursor protein. This finding suggests that axonal transport, whether fast or slow, is impaired in the terminal portion of the axon that reaches the capillaries. Some PR were also positively immunostained by the antibody against ubiquitin, anti-calbindin-D 28 K antibody, anti-parvalbumin antibody and the antibody to superoxide dismutase 1. Morphometrically, the number of PR in the anterior horns and lateral column was markedly diminished in ALS compared with controls. At the ultrastructural level, the PR consisted mostly of unmyelinated degenerated axons, and were frequently found outside the basal laminae of the endothelial cell and of the astrocytic foot processes on the opposite side of the capillary, and less often in the space between the two basal laminae. The data indicate that the fate of PR is intimately associated with the neuronal loss of the anterior horn cells and with degenerative change of nerve fibers extending from their mother neurons to the capillaries.