OBJECTIVE Immunohistochemical examination was undertaken to assess the presence of lymphocytes and lymphocyte subsets in the spinal cord in amyotrophic lateral sclerosis (ALS). METHODS Twenty-seven consecutive ALS autopsy cases and 11 consecutive disease--control autopsy cases were examined. Tissue sections were reacted with mouse monoclonal antibody to human leukocyte common antigen, or monoclonal antibody to human B-cell L26 antigen, and detected with immunoperoxidase techniques. Unfixed sections were reacted with antihuman Leu-3a and Leu-3b/CD4 or antihuman Leu-2a/CD8 mouse monoclonal antibody and then detected with peroxidase techniques. METHODS Tertiary care hospital. METHODS Amyotrophic lateral sclerosis and non-ALS control autopsy specimens. METHODS Detection of lymphocytes by histological and immunohistochemical reactivity. RESULTS Perivascular and intraparenchymal lymphocytic infiltrates were found in the spinal cord of 18 of 27 consecutive ALS autopsy cases. The lymphocytes possessed only T-cell markers; no B-cell markers could be demonstrated. T-helper cells were found in proximity to degenerating corticospinal tracts, while T-helper and T-suppressor/cytotoxic cells were demonstrated in ventral horns. Lymphocytes were present in the spinal cord of only one control specimen (multiple sclerosis) and in none of the remaining 10 control specimens. In ALS tissue, the lymphocytic infiltrates did not correlate with the rate of progression or stage of the disease or with the presence or absence of terminal infections. CONCLUSIONS T-cell lymphocytes are present in the spinal cord of patients with ALS. T-helper cells are found in proximity to corticospinal tract degeneration, while T-helper and T-suppressor/cytotoxic cells are present in ventral horns. The role of these lymphocytes remains to be elucidated.