To determine the effect of exercise on serum levels of Clara cell protein (CC16) and surfactant-associated protein A (SP-A), serum was collected from 14 healthy subjects 1 h after maximal and sub-maximal exercise. Healthy volunteers participated on separate occasions in a control (no exercise) session, simulated firefighting tasks for 30 min (n=14), and intermittent treadmill exercise at near maximal heart rates for 60 min (n=10). Serum samples and induced sputum samples were collected 1 h post exercise. Induced sputum fluid was analyzed for tumor necrosis factor alpha (TNF-alpha), an inflammatory mediator produced by pulmonary macrophages. Serum CC16 levels increased significantly with both firefighting tasks (15+/-13 microg/L vs. 9+/-4 microg/L, P=0.047) and treadmill exercise (15+/-8 microg/L vs. 9+/-4 microg/L, P<0.01). Serum SP-A concentrations did not change compared to control with either firefighting tasks (247+/-106 microg/L vs. 247+/-96 microg/L, P=0.84) or treadmill exercise (251+/-89 microg/L vs. 285+/-87 microg/L, P=0.44). TNF-alpha concentrations in sputum supernatant showed no significant difference from controls. These results show an increase in serum CC16 after exercise. This must be considered when utilizing serum CC16 to determine the presence of lung injury in settings that combine exercise and toxic exposures.