Salmeterol xinafoate, a potent, long-acting, selective beta(2)-agonist, inhibits allergen-induced asthmatic responses. To evaluate if this bronchoprotection was also associated with anti-inflammatory effects, mild asthmatic patients presenting a dual asthmatic response to allergens were randomized in a double-masked, placebo-controlled, parallel-group study to take either salmeterol 50 mu g twice daily (n = 7) or placebo (n = 6) for 2 months. At the end of the treatment period, airway inflammation was assessed by bronchoalveolar lavage and bronchial biopsies, both before and after allergen challenge. After treatment, allergen-induced responses were decreased in the salmeterol group and, to a lesser degree, in the placebo group. Postallergen and preallergen challenge, lavage total, and differential cell counts mere similar in the two groups. Before allergen challenge, bronchial biopsies of both groups indicated extensive airway inflammation with similar total inflammatory cell counts but with a higher percentage of epithelial desquamation in the salmeterol group. The allergen challenge did not modify the inflammatory variables measured except for an increase in eosinophil counts in connective tissue. Comparison of the postchallenge data of the two groups showed that counts of AA1-, HLA-DR-, and CD45ro-positive cells were reduced in the salmeterol group. When prechallenge and postchallenge data were pooled to compare the two treatments, the salmeterol group had lower numbers of CD3-, CD25-, HLA-DR-, AA1-, CD45-, and CD45ro-positive cells. In conclusion, these results confirmed the bronchodilator and bronchoprotective effects of salmeterol. They also suggested that; even though salmeterol did not modify lavage and overall bronchial biopsy cellular infiltrate, the drug apparently reduced expression of some bronchial mucosa activation cell markers. This study, however, was mainly exploratory, and the reproducibility and clinical significance of these observations require further clarification.