Sera from patients with multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), subacute sclerosing panencephalitis (SSPE), and myasthenia gravis (MG) were assayed for immune complexes. Three techniques were used: a modified Raji cell assay, the 125I-Clq polyethyleneglycol assay, and a solid-phase clq assay. Immune complex levels were elevated in sera of some patients with MS, ALS, and SSPE, but the elevations were modest when compared with active systemic lupus erythematosus (SLE). In some cases, abnormalities were detected in only one assay system; in other cases, abnormalities were detected by two or three assay systems. In MS, immune complex elevations correlated with active disease and with decreased suppressor cell activity. Of two ALS patients with antecedent poliomyelitis, one had markedly increased levels of immune complexes in two assays. In MG, levels of immune complexes did not differ from those of controls.