Airway epithelium is exposed to inhaled exogenous sources. Injury of the alveolar epithelium by cigarette smoking is presumed to be an important process in the pathogenesis of smoking-related pulmonary diseases. Current mechanistic assays that measure the toxicity of cigarette smoke focus on carcinogenesis. However, there is a need to design assays relevant to other disease processes. Oxidative stress is implicated in the pathogenesis of many respiratory diseases including chronic obstructive pulmonary disease. Therefore, we evaluated whether in vitro studies of cigarette smoking are appropriate to examine HO-1 mRNA expression. The human lung epithelial cell line A549 was exposed to the particulate fraction of cigarette smoke (Cigarette Smoke Condensate; CSC) and examined for the induction of HO-1 mRNA. HO-1 gene expression by CSC is increased dose-dependently. In comparison of the induction of HO-1 mRNA by CSC prepared from flue-cured or Burley tobacco, CSC from flue-cured tobacco seems to tend to induce an mRNA of HO-1 higher than CSC from Burley tobacco. The adaptation of HO-1 mRNA expression assay as a biologically relevant indicator of cigarette smoke-induced stress may be exemplified in this study whereby CSC derived from cigarette smoke positively correlated with an increase in HO-1 expression and the difference of the type of tobacco can be detected.