Technical Abstract: Individual animal variation occurs regarding external parasite infestation in beef cattle. Our objective was to determine if horn flies infestations present on beef cattle are associated with the single nucleotide polymorphism (SNP; T-318C) in the cytochrome P450 gene (CYP3A28) and the prolactin (PRL) promoter gene (C1286T). Sixty-four cattle were genotyped for the T-318C SNP and forty-three were genotyped for the C1286T SNP. Cattle were on either common bermudagrass (BG) or endophyte-infected tall fescue (E+) throughout the study. Individual horn fly counts on cows were recorded for 21 wks beginning in May. Horn flies were counted by walking around each cow at a set distance of 5 to 10 m. Horn fly numbers = 25 were counted individually, while numbers > 25 were counted in groups of five. Chemical fly control containing coumaphos was used wk 9 and 16 of the study. Genomic DNA was prepared from buffy coat, and three genotypes for the CYP3A28 gene and PRL gene were identified. Results found an effect of week occurred for both the T-318C (P < 0.0001) and the C1286T (P < 0.0001) SNP. Homozygous thymine cows (TT) for T-318C SNP had greater (P < 0.0001) numbers of horn flies (180.1 ± 10.9 flies) than heterozygous thymine-cystine (TC; 96.7 ± 12.4 flies) and homozygous cystine (CC; 53.5 ± 35.0 flies) cows. Cows homozygous CC for the C1286T SNP had greater (P = 0.0025) numbers of horn flies (207.7 ± 21.6 flies) than heterozygous CT (127.9 ± 14.6 flies) and homozygous TT (87.6 ± 27.3 flies) cows. A genotype x week interaction occurred for both the T-318C (P < 0.0001) and C1286T (P = 0.0018) SNP. Cattle grazing E+ tall fescue tended to have fewer horn flies than those grazing BG for both the T-318C (86.2 ± 22.4 vs. 134.0 ± 12.8 flies; P = 0.06) and C1286T (120.0 ± 18.5 vs. 162.1 ± 17.1 flies; P = 0.10) SNP. Different genotypes appear to have an effect on external parasite infestation observed on beef cows, and genetic selection of cows with these SNP could improve external parasite resistance in beef cattle.