Three-hundred and fifty patients with moderate to severe reversible obstructive airways disease (forced expiratory volume in 1 s or peak expiratory flow rate < or = 50% predicted, a 15% reversibility to inhaled salbutamol and symptomatic) were recruited into a multi-centre, multinational, double-blind, parallel-group randomized study. Two-hundred and eighty-three patients were randomized to receive 50 micrograms salmeterol twice daily or 100 micrograms salmeterol twice daily administered from a metered-dose inhaler for 3 months. Salbutamol (100 micrograms per metered actuation) was provided for symptomatic relief. Morning and evening peak expiratory flow rate (PEFR), day-time and night-time asthma symptoms and additional bronchodilator usage were recorded by the patient on a daily basis. Lung function and patient/physician assessment of treatment efficacy were recorded at scheduled clinic visits. Safety was determined by monitoring adverse events and standard biochemical, haematological and cardiovascular parameters. Salmeterol 100 micrograms twice daily was consistently superior to salmeterol 50 micrograms twice daily in morning and evening PEFR measurements (mean differences between the treatments: 10-14 l min-1 for morning, 95% CI-0, 22 l min-1, P = 0.047; and 10-15 l min-1 for evening, 95% CI 2, 22 l min-1, P = 0.023). The improvement in PEFR was independent of concurrent steroid usage, with the most marked improvement being seen in the more severe asthmatics requiring concurrent oral corticosteroids (mean differences between the treatments: 27-31 l min-1, 95% CI: 3,55 l m-1, P = 0.027).(ABSTRACT TRUNCATED AT 250 WORDS)