The effect of an extract of histamine-sensitizing factor (HSF) of Bordetella pertussis on the immune response of different strains of mice to ovalbumin (OA) was investigated with regard to optimal dose of antigen and adjuvant. It was observed that all strains of mice treated with HSF during immunization with OA demonstrated enhanced production of hemagglutinating antibodies, as compared to animals treated with antigen alone. This enhancement was generally not as great as that demonstrated when Al(OH)3 was the adjuvant. HSF also stimulated a reaginic antibody response (IgE) to OA, but not in all strains of mice. In reagin responders optimal responses were observed with high doses of both antigen and adjuvant, whereas low doses of both produced little or no response. Maximal reagin production occurred usually 14-28 days after immunization and persisted for long periods of time. An anamnestic reagin response was elicited upon secondary immunization with antigen alone, not only in mice immunized with OA and HSF but also in animals treated with OA alone. These studies demonstrate the profound effect that a microbial substance such as HSF can have on reaginic antibody production and suggest that the stimulation of IgE antibody production is the net result of a number of factors including genetic capabilities of the host, environmental influence such as adjuvants, and prior exposure to an antigen.