Pertussis toxin is an important virulence factor of Bordetella pertussis that may also contribute to the toxicity of pertussis vaccines. The effect of low doses of pertussis toxin on response to Haemophilus influenzae type b (Hib) infection was examined in infant rats. Pretreatment of rats with 10 or 100 ng of pertussis toxin increased blood bacterial concentration (P less than .01), serum endotoxin levels (P less than .01), and mortality (P less than .05) relative to saline pretreated controls challenged with 4 x 10(3) Hib intraperitoneally. The 100-ng dose of pertussis toxin, but not the 10-ng dose, increased the leukocyte count. Thus, doses of pertussis toxin less than the threshold dose for inducing leukocytosis may enhance the susceptibility of infant rats to Hib infections.