Serum Clara cell protein (CC16) and surfactant-associated protein D (SP-D) were measured in 161 workers exposed to sulphur dioxide (SO(2)) in a non-ferrous smelter. Seventy workers from a blanket manufacture served as referents. Exposure to SO(2) and tobacco smoking were associated with a decrease of CC16 and an increase of SP-D in serum. Tobacco smoking and exposure SO(2) interacted synergistically to decrease serum CC16 but not to increase serum SP-D. While further illustrating the potential of serum CC16 and SP-D, our study confirms that SO(2) can cause airways damage at exposure levels below current occupational exposure limits.