Chickens genetically selected for low (LA) or high (HA) antibody response to sheep red blood cells (SRBC) displayed a correlated change in major histocompatibility complex (MHC), so that LA chickens were 96% B¹³ and HA chickens were 96% B²¹. During a clinical outbreak of necrotic enteritis, B²¹B²¹ genotypes experienced significantly less mortality (6% vs. 13 %) compared to B¹³B¹³ genotypes. A study was carried out to assess immunological differences between LA and HA lines during exposure to Clostridium perfringens. In Experiment 1, chickens were orally gavaged with a low (10⁷ CFU/mL) or high (10⁹ CFU/mL) dose of C. perfringens. In Experiment 2, chickens were orally gavaged with live coccidia oocysts on experiment d 1, followed by 10⁷ CFU/mL C. perfringens on d 5. Unfortunately, establishment of necrotic enteritis infection was unsuccessful in both experiments as evidenced by lack of significant intestinal lesions, as well as no negative effect on bird performance. In an ex vivo study, peripheral blood mononuclear cells (PBMCs) were isolated from each genetic line, cultured, stimulated with LPS (4 h), and exposed to varying concentrations of C. perfringens α-toxin (1, 10, 100, 1000 U/L) for 2 and 4 h. Evaluation of cellular proliferation, percent cytotoxicity and immunological gene expression was carried out in a variety of experiments. Genetic lines were found to be highly divergent in all analyses.