Bronchial airway epithelial cells (BAEpC) are among the first cells to encounter M. tuberculosis following airborne infection. However, the response of BAEpC to M. tuberculosis infection has been little studied. This study investigates the response of a human BAEpC cell line, BEAS-2B cells, to infection with Mycobacterium bovis Bacille Calmette Guerin (BCG). Cultured BEAS-2B cells were infected with BCG and evaluated by various methods at various time points. Cell proliferation was evaluated by MTT assay. Distribution of cell cycle was evaluated by cellular DNA. Apoptotic cells were identified by cell death ELISA and TUNEL. Apoptosis-relevant genes were screened by microarray. Fas, Fas ligand (Fas-L) and Fas associated death domain (FADD) were evaluated by real time PCR and Western blot, and activity of caspase-3 and caspase-8 were evaluated. BCG infection of BEAS-2B cells inhibits proliferation; induces cell cycle arrest at the G₀/G₁ phase; causes apoptosis; modulates transcription of multiple apoptosis-relevant genes; promotes translation of Fas, Fas-L and FADD; up-regulates expression of Fas and FADD proteins; and increases activity of caspase-3 and caspase-8. Infection with BCG does not cause any significant change in the secretion of TGF-. The roles of Fas and FADD as mediators of BCG-induced apoptosis in BEAS-2B cells were tested by blockade of Fas and FADD expression with silencing RNA. Blockade of Fas or FADD expression results in a decreased apoptotic response to BCG infection. In conclusion, BCG induces cell cycle arrest and apoptosis in BEAS-2B cells. BCG-induced apoptosis of BEAS-2B cells via the Fas death receptor pathway.