Bordetella pertussis is the causative agent for human whooping cough. It was found that Bordetella pertussis infection caused a change in shape from flat to round in L2 cells, which are derived from rat type 2 alveolar cells. This phenomenon was reproduced using the culture supernatant of B. pertussis, and bacterium-free adenylate cyclase toxin (CyaA) was identified as the factor responsible. A purified preparation of wild-type CyaA but not an enzyme-dead mutant caused the cell rounding. It was examined whether CyaA causes similar morphological changes in various cultured cell lines. L2, EBL, HEK293T, MC3T3-E1, NIH 3T3, and Vero cells were rounded by the toxin whereas Caco-2, Eph4, and MDCK cells were not, although all these cells showed a significant elevation of the intracellular cAMP level in response to CyaA treatment, which indicates that there is no quantitative correlation between the rounding phenotype and the intracellular cAMP level. CyaA has been believed to target various immunocompetent cells and support the establishment of the bacterial infection by subverting the host immune responses. The possibility that CyaA may also affect tissue cells such as respiratory epithelial cells and may be involved in the pathogenesis of the bacterial infection is also indicated.