We previously demonstrated that Bordetella pertussis induced macrophage apoptosis and that adenylate cyclase-hemolysin expression is required for this phenomenom. In order to determine a role for other B. pertussis factors, such as pertussis toxin or the adhesins, pertactin and filamentous hemagglutinin, we compared mutants deficient in adhesin expression or purified proteins for their ability to induce cell death. We showed that only purified adenylate cyclase-hemolysin, but neither adhesins, nor pertussis toxin, killed macrophages through apoptosis. We also demonstrated that all activities of adenylate cyclase-hemolysin were required. Moreover, our results indicate that B. pertussis does not have to invade cells to be lethal.