For most patients suffering slowly progressive dementia due to diffuse brain disease, no precise cause can be uncovered. Although arteriosclerotic cerebral vascular disease is a commonly accepted diagnosis, no precise relationship has been shown between this type of dementia and underlying vascular disease. A direct relationship has been established between severity of dementia and extent of brain pathology. Although there is no predictable underlying brain morphology, for some there is evidence for infection with a "slow virus," for others impaired cerebrospinal fluid absorption, and for still others a relationship to amyloidosis. No biochemical defect has been demonstrated which cannot be explained on the basis of brain cell destruction alone. These observations indicate a variety of causes known and unknown for these so-called primary dementias. With increasing understanding, a new rationale for diagnosis and treatment of these patients will evolve.