Cigarette smoke is shown, in this study, to potentiate emphysema induced by intratracheal administration of elastase, whereas elastase alone caused minimal disease. Elastase-treated hamsters with prior or ongoing smoke exposure uniformly had severe emphysema with decreases in lung elastic recoil and increases in mean linear intercept (L(m)). In contrast, hamsters receiving elastase alone, cigarette smoke alone, or postelastase cigarette smoke developed no or barely detectable histopathologic evidence of emphysema. Lungs from these animals had normal elastic recoil and L(m). These data support the idea that cigarette smoke exposure may unmask or amplify protease-induced emphysema caused by acute lung injury.