The genetic association of CCR5 with human immunodeficiency virus-1 (HIV-1) pathogenesis is well known. The HIV-1 entry into target cells is initiated by the binding of the viral envelope glycoproteins (gp120-gp41) with the cell surface receptor (CD4) and the coreceptor (CCR5), followed by fusion of the viral and cell membranes. Genetic variants of the gene-encoding HIV-1 coreceptor are implicated in the susceptibility to HIV-1 infection. The prevalence of these mutations may vary according to population ethnicity. In the current study, characterization and frequency distribution of the HIV-related gene variants in 135 samples of the Saudi populations were conducted. Polymerase chain reaction (PCR) of 276 bp amplicons was used to rapidly detect Δ32 deletion in the initial sample of DNA. The direct sequence of 2 overlapping PCR amplicons flanking 1,059 bp was used to detect single-nucleotide polymorphisms. A single hetrozygous Δ32 deletion allele and 6 single-nucleotide polymorphisms were detected. Only one of the identified haplotypes, Taif-1, which was found in the majority of the tested sample, is identical to CCR5 wild-type alleles. Furthermore, the results of this study raised a concern about the prospective role of the mutations detected among Saudi nationals in the HIV pathogenesis and the clinical use of CCR5 antagonists, which are currently being developed as therapeutics for HIV-1 and inflammatory diseases.