Although familial factors in Alzheimer’s disease (AD) are well established, uniform family-history assessment in genetic and epidemiologic studies of AD is neededto reconcile the divergent estimates of the cumulative risk of this illness among relatives of AD probands. To answer the need, the Consortium to Establish a Registryfor Alzheimer’s Disease (CERAD) has developed a standardized Family History Assessment of ADto identify the presence of AD, Parkinson’s disease (PD), and Down’s syndrome(DS) in family members. This paper describes the use of this new assessment instrument in 118 patients with AD (estimated mean age at onset [± SD] =64.5 ± 7.7 years) and their nondemented spouses who were enrolled in 11 different CERAD sites in the U.S.The first-degree relatives of the probands with AD had a significantly greater cumulativerisk (p < 0.005) of AD or primary progressive dementia (24.8%) than did therelatives of spouse controls (15.2%). Furthermore, the cumulative risk for this disorder among female relatives of probands was significantly greater than that among male relatives. There were no differences between the families of probands and controls for the numbers of affected first-degree relativeswith PD or DS. This is the first reported multicenter family-history study of AD, andit supports earlier reports of familial factorsin AD and indicates a higher risk to female relatives of AD probands. The CERADFamily History Assessment instrument may be useful for further multicenter and epidemiologic studies designed to delineate familial factors associated with AD.