The effects of environmental tobacco smoke (ETS) on lung surfactant are difficult to determine from analysis of human and animal lung lavage due to large variations in surfactant recovery, a lack of uniformity of smoke exposure, and the difficulties inherent in analyzing milligram quantities of a multicomponent biological material. An alternative is to examine specific components of lung surfactant in a Langmuir trough with a subphase conditioned by exposure to known quantities of ETS. Pressure-area isotherms and fluorescence microscopy measurements reveal that both the minimum surface tension and respreading of model lung surfactant monolayers and the morphology of the condensed phases at high lateral pressures are changed on subphases exposed to ETS. ETS alters the distribution and fraction of crystalline lipid domains in the monolayer, which are correlated with the minimum surface tension and monolayer viscosity in pristine lung surfactant monolayers. The minimum surface tension of the dominant lipid species in lung surfactant monolayers steadily increases with increased ETS exposure, and surfactant respreading on monolayer expansion is inhibited, which may lead to an increased work of breathing and an altered distribution of alveolar fluids.