In ALS, evidence suggests immune reactions in disease pathogenesis. Although immunological changes point to adaptive immune response, whether humoral or cellular response dominates during disease course is unknown. The study aim was to evaluate humoral immune response in ALS patients during disease progression. Circulating immune complexes (CICs), IgG, and IgM in sera of ALS patients and matching controls were evaluated after each of two visits. Results showed significantly elevated CICs and IgG in ALS patient sera. CICs decreased to control levels at the second visit, yet IgG remained higher than controls. Serum IgM was within normal range. Results suggest a humoral immune response initiating adaptive immunity in ALS, however, cellular immune response needs verification.