We previously reported two large Belgian Alzheimer families, AD/A and AD/B, with autosomal dominant transmission of the disease and early onset of the disease symptoms (< 35 years). Both pedigrees were used to examine the distance between the FAD and APP gene, using informative haplotypes of two DNA polymorphisms of the APP cDNA. Furthermore, we analysed possible linkage of both families with chromosome 21 using the markers D21S16 and D21S1/S11 and several other 21 probes. We found positive LOD scores with D21S13. Pulse field gel electrophoresis helped us to prove that D21S13 and D21S16 are closely related and may in fact be regarded as one locus in the linkage analysis of Alzheimer families. Linkage data indicate that the FAD gene is most likely located near D21S13/S16, closer to the centromere.