Gastrointestinal nematodes are a major cause of disease in grazing livestock, however, individual animals differ in their response to infection. In order to identify genes whose expression correlates with resistance status, transcriptional profiling of resistance and susceptible sheep was undertaken. Transcription profiles were taken at three time points during the growth of lambs. The number of genes differentially expressed increased as animals were exposed to longer nematode challenge. Almost 300 genes, with a variety of functions, were differentially expressed overall, although genes more highly expressed in resistant animals typically had Major Histocompatibility Complex II, free radical scavenging or smooth muscle specific functions. The Ovar-DQA1 gene was 8.4 fold more highly expressed in resistant animals. This was due in part to a higher frequency of DQA1 null alleles in susceptible animals. The null allele of DQA1 was also associated with susceptibility in a separate selection flock, presenting the hypothesis that failure to present parasite antigens to immune cells led to nematode susceptibility. To test this hypothesis, commercial rams from three breeds were genotyped for the null allele of DQA1. The homozygous null allele was associated with susceptibility in only one of the three breeds tested indicating that the null allele does not cause susceptibility to intestinal parasites per se but is probably in linkage disequilibrium with additional polymorphisms in the MHC region. A combination of these polymorphisms may contribute to susceptibility in some populations. The extent of linkage disequilibrium between polymorphisms may vary from breed to breed or population to population.