Organosomatic indices, hematological indicators of stress, and histopathological lesions were quantified for over 150 incubating herring gulls (Larus argentatus) sampled in 11 colonies throughout the Great Lakes and reference colonies in Lake Winnipeg and the Bay of Fundy. Of 21 parameters assessed, significantly more differed between Great Lakes colonies and reference colonies than between the two reference colonies. Relative adrenal, kidney, and liver masses of gulls from some Great Lakes colonies were reduced and thyroid masses increased relative to gulls from reference colonies. Foci of cellular atypia were observed in the hepatocytes of two Great Lakes gulls. Chronic periportal hepatitis, lipogranulomas and vacuolation of hepatocytes, and chronic granulomatous interstitial nephritis were more prevalent or severe in gulls from Great Lakes colonies and were associated with contaminants. The kidneys of gulls from the three most contaminated locations were damaged and functionally compromised. Interstitial nephritis was likely the most functionally significant histopathological lesion. Portal-tract fibrosis, granulomatous hepatitis, and kidney tubule dilation/obstruction and splenic enlargement were more prevalent or severe at reference sites and were associated with blood-borne parasites. Amyloid deposits were observed in the spleen, kidneys, or liver of nearly half of the gulls. Associations between the prevalence or severity of lesions and contaminant levels in gull tissues or the trophic level of their diet suggest some lesions are toxicopathic. Associations were most frequently found with planar halogenated aromatic hydrocarbons and lead. The stress response, as measured by the heterophil/lymphocyte ratio, was attenuated in gulls from Areas of Concern and associated with decreased adrenal mass. Our findings suggest that adult Great Lakes gulls suffered from chronic exposure to chemical stressors in the early 1990s sufficient to modulate endocrine function and physiological processes and induce structural changes in tissues.