A murine respiratory challenge model was used to examine the induction of cellular and humoral immune responses and their role in protection against Bordetella pertussis following immunization or previous infection. Spleen cells from mice convalescing from a B. pertussis infection exhibited extensive in vitro T-cell proliferation and secreted high levels of interleukin-2 (IL-2) and gamma interferon but not IL-4 or IL-5, a cytokine profile typical of CD4+ Th1 cells. Serum from these mice had low or undetectable anti-B. pertussis antibody levels. In contrast, mice immunized with an acellular pertussis vaccine had high levels of B. pertussis antibodies and spleen cells secreting IL-5 but not gamma interferon, a profile characteristic of CD4+ Th2 cells. Immunization with an inactivated whole-cell vaccine induced both CD4+ Th1 and serum antibody responses. After exposure to a B. pertussis respiratory challenge, the convalescent mice and those immunized with the whole-cell vaccine eliminated the bacterial infection significantly faster than mice immunized with the acellular vaccine. These findings show that the selection of antigens and their form of presentation are important in determining whether the subsequent immune response is cellular, mediated by Th1 cells, or humoral, mediated by Th2 cells. In the murine model, the induction of a Th1-mediated cellular immune response appears to be a key element in acquired immunity to a B. pertussis infection.