Premenstrual exacerbation (PME) of asthma occurs during the 5-10 days leading up to the menses and can be demonstrated in about 40% of asthmatic females. Peak expiratory flow rate (PEFR) and beta2-agonist consumption were recorded during three menstrual cycles in 67 females with mild-severe asthma. All were treated with inhaled glucocorticosteroids (IGC) and beta2-agonists, as required. Following, the patients with a premenstrual reduction in PEFR > 20%, received either salmeterol, 50 microg x 2 day(-1) or placebo, in the 10 days leading up to the menses, in a randomized, double-blind, cross-over design. Thirteen patients (19.4%) showed PME (mean +/- SEM decrease in PEFR 27 +/- 2.2%) in association with a significant increase in the mean daily beta2-agonist consumption. Following administration of salmeterol, there was a complete ablation of the PME in seven patients, a partial ablation in two patients and no effect in the remaining four patients. Only one patient showed a partial ablation of the PME following placebo. There was also a significant decrease in the beta2-agonists consumption in the responders. About 20% of the women with asthma, under chronic IGC treatment, had PME of asthma. In 54% of them, it could be prevented by the use of long-acting bronchodilators (LABD) during the 10 days leading up to the menses, and partially prevented in another 15%.