Salmonellosis is a zoonotic disease that is problematic for both animal production and food safety. A novel genetic cross, named the Iowa Salmonella response resource population (ISRRP), was established to elucidate the genetic control of resistance to Salmonella enteritidis (SE) colonization in young chicks, to characterize unique resistance alleles, and to estimate gene interaction effects. Outbred broiler sires were mated with dams of diverse, highly inbred, light-bodied lines to produce an F(1) generation that was informative for all heterozygous alleles of the sires. Mating F(1) sires back to dams of the corresponding inbred line produced a backcross generation. To mimic the natural route of exposure and thus afford the opportunity to investigate mucosal immunity, pathogenic SE were inoculated into the esophagus of day-old chicks. After 1 week, the SE colonizing the cecal lumen and the spleen were enumerated. Candidate genes were selected for analysis based upon one of the two criteria. Functional candidates were genes with reported activity related to the tested traits. Positional candidates were genes mapped near microsatellites that were linked, in other phases of this project, with antibody levels to SE vaccine. Broiler sire alleles of the MHC class I, NRAMP1, PSAP, and IAP1 genes showed association with SE colonization in the F(1) generation of this novel disease resistance resource population.