Linkage analysis was used to search the genome for chromosomal regions harboring familial Alzheimer's disease genes. Markers on chromosome 14 gave highly significant positive lod scores in early-onset non-Volga German kindreds; a Zmax of 9.15 (θ=0.01) was obtained with the marker D14S43 at 14q24.3. One early-onset family yielded a lod score of 4.89 (θ=0.0). When no assumptions were made about age-dependent penetrance, significant results were still obtained (Zmax=5.94, θ=0.0), despite the loss of power to detect linkage under these conditions. Results for the Volga German families were either negative or nonsignificant for markers in this region. Thus, evidence indicates a familial Alzheimer's disease locus on chromosome 14.