Some dementias, such as Creutzfeldt-Jakob disease, may result from transmissible agents. To assess the possibility of a blood-borne transmissible agent in Alzheimer's disease (AD), we compared informant-reported history of blood transfusions among 326 newly recognized probable AD cases and 330 control subjects of similar age and sex, randomly selected from the same health maintenance organization population. Since risk of AD is increased in persons with apolipoprotein E epsilon 4 (APOE-e4) alleles, we examined whether the transfusion-AD relationship varies by APOE genotype. Transfusion was more frequent among controls (17.9%) than cases (12.0%) in the overall group (crude odds ratio = 0.62; 95% confidence interval = 0.40, 0.97). Similar risks were seen for transfusions occurring < or = or > 10 years before the reference year. Stratified analysis by APOE-e4 genotype showed no effect modification. Logistic regression adjusting for age, sex, education, and presence of e4 did not change the transfusion-AD association. We conclude that a history of blood transfusion is not associated with increased risk of AD, nor does consideration of APOE-e4 status modify that conclusion.