The aims of study were to identify high (H), medium (M), and low (L) hypothalamic-pituitary-adrenal axis (HPAA) stress responsive sheep using ' E. coli' endotoxin lipopolysaccharide (LPS), and to assess associations between variable stress responsiveness and immune responsiveness (IR), and hepatic gene expression. Sheep were challenged 'iv' with LPS and identified as H, M, L stress responders based on their estimated breeding values for peak cortisol concentration 4-hours post-challenge. Liver biopsies were collected from the H and L responders for hepatic gene expression studies. Unexpectedly, the IR was not significantly different between H and L stress responders. However, there was a significantly higher cell-mediated IR and a lower antigen-specific primary IgG response (P <= 0.05) in H and L stress responders when compared to M stress responders. Similar hepatic gene expression profiles between the H and L HPAA responders suggests that hepatic gene expression doesn't contribute significantly to this stress response phenotype.