Clinical benefits have been shown to occur when using the long-acting beta2-agonist formoterol 4.5 microg for as-needed medication rather than terbutaline 500 microg in patients with unstable asthma taking an inhaled corticosteroid. This study compared their effects on health-related quality of life and the relation with conventional clinical indices in the same population. 362 asthmatics were randomized to use either formoterol 4.5 microg or terbutaline 500 microg as needed, both inhaled via Turbuhaler. The Asthma Quality of Life Questionnaire (AQLQ) was practised at enrolment and completed by 341 patients after randomization and at 4, 8, and 12 weeks. Clinical indices were measured at the same time points. Mean overall AQLQ scores were comparable at baseline, being 4.90 in the formoterol and 4.82 in the terbutaline group and improved during treatment by 0.41 and 0.17 units, respectively (mean difference 0.24, 95% CI 0.08, 0.39, P<0.005). Mean improvement in the symptom domain was 0.49 units when using formoterol. Correlations between changes in clinical indices and changes in AQLQ scores during the 12-week period were weak (maximum r value=0.37). When used for as-needed medication, formoterol 4.5 microg provided an improvement in asthma-specific quality of life and to a somewhat greater extent than the widely used terbutaline 500 microg. The symptom domain in AQLQ showed almost 0.5 units improvement after formoterol, a change that is considered to be clinically relevant.