Hallmark lesions of Alzheimer disease (AD) are filled with reactive immunocompetent microglia, suggesting that immunological aderrations may participate in the pathophysiology of this disorder. If immune-mediated processes are closely linked to neuronal breakdown, it would be or importance to have a reliable means to detect these processes. Cerebrospinal fluid (CSF) antibodies are discussed as such potential sources. The seredipitous use of the developing rat central nervous system (CNS) unexpectedly demonstrated that some AD CSF recognize amoeboid microglial cells. Similarly, AD CSF specifically stains activated microglia and neural macrophages in experimentally induced lesions. A cell-culture technique is described that allows rapid screening of CSF antibodies. Examination of CSF from a diversified dementia population revealed that AD CSF, in contrast to other dementia CSF, displayed remarkable selectivity toward microglial cells. Cortical biopsies from patients suspected to have AD were incubated with the patient's own CSF and that of confirmed AD patients. Both CSF samples recognized microglial cells in the cortical biopsy. AD CSF microglial antibodies appear to be significant in view of the increasing association between microglia and neuro degenerative processes in AD. These findings add further support to the concept that inflammation and similar immune mechanisms may contribute to to AD pathogenesis.