Technical Abstract: Understanding mechanisms of resistance to gastrointestinal nematodes is important in developing effective and sustainable control programs. A resource population of Angus cattle consisting of approximately 600 animals with complete pedigree records has been developed. The majority of these animals were completely characterized for their resistance to natural challenge by gastrointestinal nematodes. As the first step towards understanding the molecular basis of disease resistance, we investigated expression profiles of 17 cytokines, cytokine receptors, and chemokines using real-time RT-PCR in animals demonstrating resistance or susceptibility to pasture challenge. The animals exposed to natural infection for approximately 6 months were treated to remove existing parasites and then experimentally challenged with both Ostertagia ostertagi and Cooperia oncophora. The mRNA expression profiles of these genes in abomasal and mesenteric lymph nodes, fundic and pyloric abomasa, and small intestine were compared between resistant and susceptible animals. Resistant heifers exhibited elevated expression of inflammatory cytokines such as TNF', IL-1', and MIP-1' in fundic and pyloric abomasa 7 days post infection. Expression levels of IL-10, PIGR, and WSX-1 were also 2.7 to 19.9 folds higher in resistant than susceptible heifers in these tissues. No difference in expression of IFN-', IL-2, IL-4, IL-6, IL-8, IL-15 and IL-18 was observed between the two groups. The expression of MIP-1' , IL-6, and IL-10 was also elevated in small intestines in resistant animals. In contrast, little difference in expression of these genes was detected between resistant and susceptible groups in the draining lymph nodes. These data indicate that resistant animals can better maintain inflammatory responses at the site of infection, suggesting a possible novel mechanism of resistance.