The cerebrospinal fluid (CSF) was examined in 90 amyotrophic lateral sclerosis (ALS) patients and in 50 age-matched normal controls. Total protein concentration was significantly higher in ALS patients than in normal controls. CSF IgG and albumin, quantitatively determined by single radial immunodiffusion, were significantly increased in ALS. No difference in serum concentrations was observed between ALS patients and normal controls. On isoelectric focusing a clear-cut “fingerprint” pattern was observed in 11 of 12 cases. These findings support the hypothesis that blood-brain barrier damage occurs in ALS. The finding of a higher mononuclear cell count in young ALS patients is briefly discussed in the light of the hypothesis that an exogenous agent might be of some relevance in pathogenesis. An alteration of at least one of the CSF parameters considered was found in 45.5% of ALS cases.