In this study the attachment, detachment and proliferation of the A549 human alveolar epithelial cell line was examined in an in vitro model of cell injury the effects of exposure to cigarette smoke and its condensates on these assays of epithelial function were assessed. In addition a comparison of the effects of cigarette smoke on the bronchial cell line, BEA-2B or freshly isolated rat type II cells, and the protective effects of the antioxidants were also studied. Whole and vapour phase cigarette smoke decreased ⁵¹Cr-labelled A549 epithelial cell attachment in a dose dependent manner. The condensates prepared from both types of cigarette smoke increased cell detachment and decreased cell proliferation, as assessed by the uptake of [³H] thymidine by A549 epithelial cells. Both freshly isolated rat type II alveolar epithelial cells and cells of the bronchial epithelial cell line, BEA-2B, showed enhanced susceptibility to the injurious effects of cigarette smoke condensates when compared with the A549 epithelial cell line. The enzymatic antioxidants superoxide dismutase and catalase, when present extracellularly, gave partial protection against the effects of cigarette smoke or condensate exposure on cell attachment, detachment and proliferation. However extracellular reduced glutathione, in physiological concentrations (400 μM), conferred total protection against cigarette smoke or condensate induced cell injury. Depletion of intracellular reduced glutathione also enhanced the epithelial cell detachment produced by cigarette smoke condensates. The oxidant hydrogen peroxide also decreased A549 epithelial cell attachment and increased cell detachment, which was prevented by the addition of reduced glutathione.