BACKGROUND.: The African American Hereditary Prostate Cancer (AAHPC) Study was designed to recruit families with early-onset disease fulfilling criteria of ≥4 affected. METHODS.: We present a ~10 cM genome-wide linkage (GWL) analysis on 77 families including 254 affected and 274 unaffected genotyped. RESULTS.: Linkage analysis revealed three chromosomal regions with GENEHUNTER multipoint HLOD scores ≥1.3 for all 77 families at 11q22, 17p11, and Xq21. One family yielded genome-wide significant evidence of linkage (LOD=3.5) to the 17p11 region with seven other families ≥2.3 in this region. Twenty-nine families with no-male-to-male (MM) transmission gave a peak HLOD of 1.62 (α=0.33) at the Xq21 locus. Two novel peaks ≥0.91 for the 16 families with ‘>6 affected’ occurred at 2p21 and 22q12. CONCLUSIONS.: These chromosomal regions in the genome warrant further follow-up based on the hypothesis of multiple susceptibility genes with modest effects, or several major genes segregating in small subsets of families.