Expression of Le^Y, a difucosylated type 2 chain determinant, has been previously identified as a characteristic of cells undergoing apoptosis. Immunohistochemistry using an antibody for Le^Y, as well as nick-end labeling for the detection of DNA breaks, was done on cervical spinal cord sections from ten patients with amyotrophic lateral sclerosis (ALS) and nine patients who had died from other causes. Le^Y-positive immunoreactivity was seen in the motor neurons of seven ALS cases, but in none of the other cases. Nickend labeling was also positive in four ALS cases. Double staining of motor neurons by anti-Le^Y antibody and nick-end labeling was shwon in these cases. Other Le^Y-positive structures, such as reactive astrocytes and fatladen microglia/macrophages in the lateral and anterior columns, were negative for nick-end labeling. These results suggest that the mechanism of cell death in the spinal motor neurons of ALS may be apoptosis.