The CCR5-Delta32 genotype is known to influence HIV-1 transmission and disease. We genotyped 1301 US women of various races/ethnicities participating in the HIV Epidemiologic Research Study. None was homozygous for CCR5-Delta32. The distribution of heterozygotes was similar in HIV-1 infected and uninfected women. Thirty-seven (11.8%) white, 28 (3.7%) blacks/African Americans (AA), seven (3.3%) Hispanics/Latinas, and one (6.6%) other race/ethnicity were heterozygous. The frequency of heterozygotes differed among sites for all races combined (P = 0.001). More heterozygotes were found in AA women in Rhode Island (8.9%) than in the other sites (3.1%) (P = 0.02), while heterozygosity in white women was most common in Maryland (28.6%) (P = 0.025). These regional differences could be accounted for by racial admixture in AAs, but not in whites. Regional variations should be considered when studying host genetic factors and HIV-1 in US populations.