Leukotrienes (LT) and platelet-activating factor (PAF) can increase nonspecific airway reactivity in normal subjects, and they have been proposed as putative mediators of asthma. Alveolar macrophages (AM), which have receptors for and synthesize leukotrienes and PAF, also may play a role in the pathogenesis of asthma. The present study was designed to determine the effects LTD₄ and PAF have on bronchoalveolar lavage (BAL) fluid and cells, including AM eicosanoid and PAF synthesis, and to relate them to changes in nonspecific airway reactivity. Airway reactivity to methacholine was measured in healthy, male volunteers at least 2 days before and 6 h, 1, 3, and 7 days after inhaling either LTD₄ or PAF. At least 3 wk later subjects inhaled in random order either methacholine or the mediator to which they were previously exposed, and BAL was performed the next day. This sequence was repeated with the other chemical 3 wk or more later. LTD₄ inhalation increased airway reactivity and stimulated AM thromboxane synthesis while it reduced stimulated AM LTB₄ synthesis. LTD₄ did not affect the number or percentage of BAL cells or the BAL fluid protein and histamine concentrations. PAF inhalation increased airway reactivity and the proportion of neutrophils and eosinophils recovered by BAL, but it did not alter AM eicosanoid and PAF synthesis or the BAL fluid protein and histamine concentrations. A relationship was identified between the PAF-induced increase in airway reactivity and the percentage of BAL neutrophils, but no correlation was found between LTD_4⁻ or PAF-induced changes in airway reactivity and stimulated AM eicosanoid or PAF synthesis. Thus, inhaled LTD₄ and PAF can affect both the bronchoalveolar milieu and airway reactivity of normal subjects. However, it is not clear from this study which changes in the bronchoalveolar milieu are causally related to the mediator-induced increase in airway reactivity.