Most clinical trials in asthma have focused on outcomes that are primarily of importance to the clinician. Very few have assessed whether patients feel better and can function better in day-to-day activities. The aim of this study was to compare the effects of salmeterol (50 micrograms twice daily), salbutamol (200 micrograms four times a day), and placebo on asthma-specific quality of life and to relate the findings to conventional clinical asthma outcomes. The study was a 12-wk multicenter, double blind, randomized, placebo-controlled crossover trial with each trial medication taken for 4 wk. The subjects were 140 adults with mild to moderate asthma enrolled from 14 respiratory clinics across Canada. Outcome measures were: (1) the Asthma Quality of Life Questionnaire and spirometry at the end of each treatment period; and (2) daily asthma symptoms, morning and evening peak expiratory flow rates (PEFRs), and rescue salbutamol use during the last 14 d of each treatment period. Asthma-specific quality of life, both overall and for the individual domains (activity limitation, symptoms, emotional function, and exposure to environmental stimuli) was better with salmeterol than with placebo (p < 0.0001), and better with salmeterol than with salbutamol (p < 0.001). In both comparisons, differences were not only statistically significant, but most were also clinically important. There were moderate correlations between change in quality of life and change in clinical outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)