Studies with two monoclonal antibodies reactive with galactolipids suggest that there is a marked loss of these compounds in the brains of patients with Pick's disease. Quantitative assays, immunocytochemical studies, and thin-layer chromatography confirm that both galactocerebrosides and sulfatides are selectively lost in this condition. This finding appears to be specific for Pick's disease, distinguishing it from Alzheimer's disease and other dementing disorders.