We previously reported that the monoclonal antibody Alz-50 recognizes a protein (A68) with an apparent molecular weight of 68,000 daltons in the brains of patients who died with Alzheimer's disease, but not in brain tissue from individuals free of neurological disease. We now report that substantial quantities of this protein are found in brain tissue only from patients with Alzheimer's disease. Although trace amounts of A68 may be detected in cases of Guam-Parkinson dementia complex and Pick's disease, accumulation of A68 in neuronal perikarya and particularly in neuronal processes appears to be a unique feature of Alzheimer's disease. A68 can readily be detected in cerebrospinal fluid after concentration and partial purification. These data, combined with the quantitation of immunoreactivity in other neurological diseases, suggest the usefulness of detection of A68 in cerebrospinal fluid for diagnosis of Alzheimer's disease.