Biomarkers of toxicity are usually altered before the onset of functional changes or clinical manifestations. Peripheral biomarkers of toxicity present an additional advantage in that they can be applied on easily accessible biological materials (blood or urine). They represent useful tools that can be used for identifying subjects or groups at risk in the industry or environment, or for establishing acceptable exposure levels. In the case of the kidney, for instance, a relatively large battery of peripheral markers has been developed during the last decade. These markers are either constituents of the renal parenchyma whose urinary excretion can signal lesions or an abnormal secretion, or plasma proteins reflecting the integrity of nephron structures involved in their selective filtration or reabsorption. The epidemiological application of these tests has revealed that widespread occupational or environmental pollutants such as lead, cadmium, crystalline silica or perchloroethylene may cause very early effects on different segments of the nephron. In the case of the lung, we have recently identified a lung toxicity biomarker applicable not only on bronchoalveolar lavage fluid but also or sputum provided some precautions are taken. This biomarker called Clara cell protein (CC16) is a kDa protein secreted in the respiratory tract by the non-ciliated Clara cells known for their vulnerability to toxic insult. Studies on occupationally exposed workers and experimental animals indicate that the assay of CC16 in serum is a sensitive and a relatively specific test to detect early acute or chronic effects of toxicants on the tracheobronchial tree. The ultimate goal, however, is the development and validation of biomarkers that have a sufficient toxicological relevance to be used for health risk assessment. It is thus of premier importance to establish in health significance of early biomarkers of toxicity by determining to what extent they reflect critical steps in, and are predictive of the development of a chronic and irreversible disease.