The cortisol stress response to capture was investigated in two species of fish (Perca flavescens and Esox lucius) from sites polluted by high levels of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and mercury, and from reference sites in the St. Lawrence river system. Fish from the reference sites exhibited the normal elevation of serum cortisol in response to the acute stress of capture and had large pituitary corticotropes. In contrast, fish from the most polluted sites were unable to increase their serum cortisol in response to the acute stress of capture and their pituitary corticotropes were atrophied. These results suggest that a life-long exposure to chemical pollutants may lead to an exhaustion of the cortisol-producing endocrine system, possibly as a result of prolonged hyperactivity of the system.