A population of eastern grey kangaroos (Macropus giganteus) inhabiting heathland and farmland surrounding an aluminum smelter at Portland, Victoria, Australia, exhibited clinical signs of lameness. An investigation was undertaken to determine the cause of this lameness. Hematology, necropsy, histopathology, fecal egg count, total worm count, reproductive status, and the population age range were examined and failed to reveal any additional underlying disease state. The specific problem of lameness was addressed with bone histopathology, radiography, quantitative ultrasonography, microradiography, and multielement analysis of bone ash samples. The significant lesions observed were: osteophytosis of the distal tibia and fibula, tarsal bones, metatarsus IV, and proximal coccygeal vertebrae; osteopenia of the femur, tibia, and metatarsus IV; incisor enamel hypoplasia; stained, uneven, and abnormal teeth wear; abnormal bone matrix mineralization and mottling; increased bone density; and elevated bone fluoride levels. Microradiography of affected kangaroos exhibited “black osteons,” which are a known manifestation of fluorosis. Collectively, these lesions were consistent with a diagnosis of fluorosis.