This study compared the efficacy of inhaled salmeterol (SM) 50 μmg twice a day with SM 100 μmg once a day (at night) and placebo in patients with poorly controlled nocturnal asthma despite treatment with corticosteroids, oral long-acting bronchodilators, or both. This was a two-center, double-blind, randomized, crossover study with three treatment periods, each of 3 weeks’ duration. The first treatment period was preceded by two 1-week run-in periods, and the last treatment period was followed by a 2-week follow-up period. In the three treatment periods, patients received either SM 50 μmg twice a day, SM 100 μmg nightly, or placebo, in randomized order. Salbutamol metered-dose inhaler was given as relief medication. Of the 41 randomized patients, 38 were evaluable for more than one treatment period. Efficacy and safety were determined by daily record card data: morning and evening peak expiratory flow rates (PEFR), daytime and nighttime asthma symptom scores, and rescue salbutamol use. At clinic visits, FEV1 and FVC were measured, and the physicians’ and the patients’ respective assessments of the study mediation were noted. The study showed that the two doses, SM 50 μmg twice a day and SM 100 μmg nightly, were equally effective in controlling nocturnal asthma symptoms and were significantly better than placebo. SM was well tolerated, and no unexpected problems were revealed. The adverse events reported during this study were related either to the patient's underlying disease or to an intercurrent respiratory infection.