Changes in health-related quality of life (HRQoL) were evaluated in patients with chronic obstructive pulmonary disease (COPD) following treatment with placebo, salmeterol 50 microg twice a day or 100 microg twice a day by metered-dose inhaler. Patients completed the disease-specific St. George's Respiratory Questionnaire (SGRQ) and the Medical Outcomes Study Short Form 36 (SF-36) at baseline and after 16 wk of treatment. Data from 283 patients (95 patients in the placebo group and 94 in each salmeterol group) were available for HRQoL analysis. Apart from a small difference in ages, all treatment groups were well matched at baseline in terms of forced expiratory volume in one second (FEV1) and HRQoL scores. Compared with placebo, salmeterol 50 microg twice a day was associated with significant improvements in SGRQ "Total" and "Impacts" scores which exceeded the threshold for a clinically significant change. This was not seen with salmeterol 100 microg twice a day. Changes in SGRQ and SF-36 scores correlated. They also showed a weak but significant relationship with FEV1. This study has shown that a modest change in lung function may be associated with clinically significant gain in health and well-being in COPD patients.