The northern fowl mite (NFM) is a blood-feeding ectoparasite of birds and a serious pest of poultry in North America. Populations of NFM on laying hens follow a stereotypical pattern of rapid growth and subsequent decline 4-6 weeks later. An immune response by the host is suspected to cause this population deflection. The immune response of NFM-infested hens was characterized by analysis of peripheral blood samples and skin samples at mite feeding sites, as well as genotyping of immunological loci. Infested birds developed mite-specific antibodies and white blood-cell populations were up-regulated following establishment of the parasite. Examination of host skin revealed epidermal cells increased in size and number in conjunction with scabbing at the skin surface. These events caused the surface—capillary distance to increase beyond the length of protonymph mouthparts initially, and adult female mouthparts ultimately, leading to mite starvation. Destructively sampled mite populations showed protonymphs failed to develop into adults and female reproduction decreased. The immunogenetic basis of mite resistance was determined by comparison of the major histocompatibility complex (MHC) between inbred lines of hens. The MHC is a tightly linked set of genes critical to the acquired immune response of vertebrates. The chicken line homozygous for the B15 MHC haplotype was consistently susceptible to NFM, relative to the other lines tested. Genotyping of outbred, commercial birds confirmed the association of the B15 haplotype with mite susceptibility. These studies demonstrated a connection between the immune response of the chicken and the population dynamics of NFM.