Leukotriene (LT) B4 is a potent leukocyte chemotaxin that increases bronchial responsiveness in animal models. In a double-blind, placebo-controlled crossover study we examined the effects of LTB4 on lung function, bronchial responsiveness, and blood leukocyte counts in six normal subjects and in six subjects with mild asthma who inhaled mean +/- SEM doses of 17.6 +/- 3.4 and 18.2 +/- 1.9 microg LTB4, respectively, or placebo. There were no significant changes in specific airway conductance or bronchial responsiveness in either normal subjects or asthmatics for as long as 24 h after inhalation. In the normal subjects, LTB4 rapidly reduced blood neutrophil counts to 19.8 +/- 6.3% of baseline at 5 min (p = 0.0003 compared with placebo), followed by a neutrophilia of 307 +/- 40% of baseline at 30 min (p = 0.007). Similar changes occurred in asthmatics, with a neutropenia at 5 min (69.6 +/- 5.8%; p = 0.003) and a neutrophilia at 30 min (183 +/- 17.2%; p = 0.037). The neutrophilia was not sustained in either subject group, with values being no different from that of placebo by 6 h. The asthmatics had significantly less neutropenia (p = 0.005) and less neutrophilia (p = 0.018) than did the normal subjects. Placebo inhalation had no effect on any parameter in either group. The smaller neutrophil responses in asthmatics may reflect desensitization of blood neutrophils in vivo because of chronic exposure to endogenous LTB4.