Exposure to Pseudomonas aeruginosa triggers the apoptotic cell death of Chang epithelial cells, and this depends on the expression of both the CD95 receptor and CD95 ligand. In lymphocytes CD95-mediated apoptosis is paralleled by the activation of outwardly rectifying Cl- channels. The present study was performed to explore whether P. aeruginosa-induced apoptosis of Chang epithelial cells is paralleled by activation of Cl- channels. According to whole-cell patch-clamp recordings, exposure of Chang epithelial cells to P. aeruginosa does lead to rapid activation of an outwardly rectifying Cl- -selective current. The current is inhibited by the Cl- channel blocker NPPB. Exposure of Chang epithelial cells to P. aeruginosa led to a significant decrease of cell membrane capacitance by 6%, pointing to a decrease in cell volume by 7%. Exposure to P. aeruginosa depolarized the mitochondrial membrane potential indicating apoptotic cell death. The decline of mitochondrial membrane potential was not significantly affected by NPPB. In conclusion, P. aeruginosa-induced apoptosis of Chang epithelial cells is paralleled by activation of Cl- channels. Activation of the channels participates in the alteration of cell volume but is not a prerequisite for P. aeruginosa-induced apoptosis.