This study validated a QTL for host response to PRRS virus previously discovered in the PRRS Host Genetics Consortium PRRS-CAP. Five trials of 200 commercial crossbred pigs, from 3 genetics companies, were infected between 18 and 28 days of age with virus isolate NVSL 97-7985. Blood samples and body weights were collected up to 42 days post infection (dpi). Whole genome analyses of 60k Beadchip genotypes focused on viral load (VL = area under the curve for log-transformed RT-PCR based serum virus from 0-21 dpi) and weight gain (WG = gain from 0-42 dpi). Associations were identified using Bayes-B of GenSel. Previous analysis of the first 3 trials identified a 33-SNP region on SSC4 that explained 15.7% and 11.2% of genetic variation for VL and WG. That region was supported in the analysis of all 5 trials, explaining 22.6% of the genetic variance for VL and 19.2% for WG. Correlations of GEBV predicted for the 33-SNP region using estimates from the first 3 trials, with whole genome true BV in trials 4 and 5 were 0.24 and 0.33 for VL and 0.24 and 0.41 for WG, compared to expected accuracies of 0.5 if individual phenotype was available, which requires disease exposure. In conclusion, this region on SSC4 explains a substantial proportion of genetic variation in response to challenge with this specific viral strain. This work was supported by PRRS CAP, USDA NIFA Award 2008-55620-19132, NRSP-8 Swine Genome and Bioinformatics projects, the National Pork Board and breeding companies in the PRRS Host Genetics Consortium.