Cigarette smoke extract showed differential effects on intracellular reduced glutathione levels in alveolar epithelial cells and in primary human small airway epithelial cells. A. Transformed alveolar epithelial cell lines of our interest; H1299, A549, H441, L2 and MLE-15 were treated with cigarette smoke extract (1.0–5.0%) for 24 hr. After incubation period, GSH levels were measured by the Tietze method. Although, the baseline GSH levels were varied amongst the cell lines, CSE decreased GSH levels dose-dependently at 24 hr in all five epithelial cell lines. The most resistant cell line H1299 had higher baseline GSH levels whereas the least resistant MLE-15 had lower baseline GSH levels. B. Primary human small airway epithelial cells (SAEC) were also treated with cigarette smoke extract (0.2–1.0%) for 4 and 24 hrs, and GSH levels were measured. CSE dose- dependently decreased GSH levels in SAEC at 4 hr, where as the levels were increased dose-dependently at 24 hr. Data is representative of 3 separate experiments ± SEM. *p < 0.05, #p < 0.01, and §p < 0.001 compared with corresponding control. CSE: cigarette smoke extract.