Alzheimer's disease, an autosomal dominant disorder, is characterized by the presence of neurofibrillary tangles and senile extracellular plaques in the brain of affected individuals. An amyloid beta protein has been isolated from the core of these plaques, and the gene encoding this protein has been mapped to region q11.2 to q22.2 of chromosome 21. Independent linkage studies have shown that the locus responsible for familial Alzheimer's disease also maps to the long arm of chromosome 21. It is thus very tempting to speculate that a defect (or defects) of the amyloid beta protein gene is the cause of Alzheimer's disease. For this reason, we have done association studies between Alzheimer's disease and restriction fragment length polymorphisms of the amyloid beta protein gene locus. We report a study of six restriction fragment length polymorphisms at the human amyloid beta protein gene locus. Several haplotypes constitute very informative marker systems for this region of chromosome 21. One of the six polymorphisms, a 6.6/7.3 kb (kb = 10(3) base-pairs) EcoRI restriction fragment length polymorphism, is loosely associated with the presence of Alzheimer's disease in a population of 34 subjects.