The histamine-sensitizing factor (HSF) of Bordetella pertussis was isolated in a highly purified form. In addition to inducing profound sensitization to histamine, it also caused a significant lymphocytosis and produced an enhancement of reaginic antibody production in animals upon immunization with antigen. Biologically active doses of HSF produced significant pathological changes in mice including congestion and edema of the lung and a marked depletion of cells in the thymus, white pulp of the spleen, and lymph nodes. The lymphocytosis and histological changes in the lungs and lymphoid organs were observed in different strains of mice injected with HSF (even those that are resistant to its histamine-sensitizing effects). Heating HSF at 80 degrees C for 30 min, a treatment that destroys histamine sensitizing and lymphocytosis promoting activities, completely abolishes the ability to induce the changes observed in the lungs and lymphoid organs.