The gene encoding the beta-amyloid precursor protein has been assigned to human chromosome 21, as has a gene responsible for at least some cases of familial Alzheimer disease. Linkage studies strongly suggest that the beta-amyloid precursor protein and the product corresponding to familial Alzheimer disease are from two genes, or at least that several million base pairs of DNA separate the markers. The precise location of the beta-amyloid precursor protein gene on chromosome 21 has not yet been determined. Here we show, by using a somatic-cell/hybrid-cell mapping panel, in situ hybridization, and transverse-alternating-field electrophoresis, that the beta-amyloid precursor protein gene is located on chromosome 21 very near the 21q21/21q22 border and probably within the region of chromosome 21 that, when trisomic, results in Down syndrome.