Polybrominated diphenyl ethers (PBDEs), used as commercial flame-retardants, are bioaccumulating in threatened Pacific salmon. However, little is known of PBDE effects on critical physiological functions required for optimal health and survival. BDE-47 and BDE-99 are the predominant PBDE congeners found in Chinook salmon collected from the Pacific Northwest. In the present study, both innate immunity (phagocytosis and production of superoxide anion) and pathogen challenge were used to evaluate health and survival in groups of juvenile Chinook salmon exposed orally to either BDE-47 or BDE-99 at environmentally relevant concentrations. Head kidney macrophages from Chinook salmon exposed to BDE-99, but not those exposed to BDE-47, were found to have a reduced ability in vitro to engulf foreign particles. However, both congeners increased the in vitro production of superoxide anion in head kidney macrophages. Salmon exposed to either congener had reduced survival during challenge with the pathogenic marine bacteria Listonella anguillarum. The concentration response curves generated for these end points were nonmonotonic and demonstrated a requirement for using multiple environmentally relevant PBDE concentrations for effect studies. Consequently, predicting risk from toxicity reference values traditionally generated with monotonic concentration responses may underestimate PBDE effect on critical physiological functions required for optimal health and survival in salmon.