Clinical and neuropathological similarities between Alzheimer disease and the transmissible spongiform encephalopathies have sparked intensive investigation of the role of nearly every arm of the immune system in the etiology and pathogenesis of Alzheimer disease. These endeavors have yielded intriguing results but no clear-cut answers. Studies of humoral and cellular immune function in patients with dementia of the Alzheimer type (DAT), immunohistochemical examinations of Alzheimer brain tissue and HLA typing of both sporadic and familial DAT are reviewed. Sporadic DAT appears to be associated with the complement allotype C4B2 in the major histocompatibility complex, which is linked very closely to HLA. Mechanisms for the role of complement in the pathogenesis of DAT are postulated.