Cigarette smoke extract differentially caused cytotoxicity in a variety of alveolar epithelial cells and in primary human small airway epithelial cells. A. Various alveolar epithelial cells such as human lung cancer cells (H1299), human adenocarcinoma cells (A549), human lung epithelial cell from papillary adenocarcinoma patient (H441), rat lung epithelial cells (L2), and murine type II epithelial cells (MLE-15) were exposed to different concentrations of cigarette smoke (1R3F) extract (1.0–10.0%) for 24 hr, and % cytotoxicity induced was measured as lactate dehydrogenase release. CSE differentially induced cytotoxicity in concentration dependent manner in all the five epithelial cell lines. Amongst the five cell lines studied, H1299 cells were most resistant and MLE 15 cells were the least resistant. B. Primary human small airway epithelial cells (SAEC) were exposed to different concentrations of cigarette smoke (1R3F) extract (0.2–5.0%) for 24 hr and percentage (%) cytotoxicity induced was measured as LDH release. CSE dose-dependently induced LDH release in SAEC. Data represent mean ± SEM of 3 experiments. *p < 0.05, #p < 0.01, and §p < 0.001 compared to control group. CSE: cigarette smoke extract.