In this study, the levels of anti-Fas antibodies were evaluated in patients with amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Sera from 25% of patients with sporadic ALS (sALS) and 22% of patients with familial ALS (fALS) contained abnormal levels of anti-Fas antibodies compared with normal controls. Half of patients with Parkinson's disease (PD), but no patients with Alzheimer's disease (AD), had abnormal levels of anti-Fas antibodies. There was no correlation between the antibody levels of patients with ALS and the length or stage of their disease. These data demonstrate that the peripheral immune system is activated as reflected by anti-Fas antibodies in ALS, but this activation is not specific to ALS.