Immunization of mice with a whole-cell pertussis vaccine or with the purified, detoxified lymphocytosis-promoting factor (LPF) of Bordetella pertussis resulted in an increased in vitro proliferative response to LPF in immune lymph node cells. The proliferative response was detected above the nonspecific mitogenic activity of LPF. That the proliferative response of the immune lymph node cells was a demonstration of a specific cell-mediated immunity to LPF was supported by the following: (i) the specificity of the response to the immunizing antigen; (ii) the ability of chemically modified, nonmitogenic LPF to induce proliferation in immune lymph node cells; and (iii) a dependence on T-cells for the demonstration of the proliferative response of immune cells to LPF. Immunization of mice with protective doses of detoxified LPF resulted in serum antibody and cell-mediated responses to LPF. Immunization of mice with protective doses of whole-cell pertussis vaccine resulted in a cell-mediated response but not a detectable antibody response to LPF. The LPF of B. pertussis is believed to play an important role in pathogenesis and immunity in pertussis, and the demonstration of a cell-mediated immune response to LPF suggests a possible role for cell-mediated immunity to LPF in protection from pertussis disease.