Because biological indicators alone do not adequately represent the comprehensive health status of a patient with asthma, we also assessed patients' health-related quality of life (HRQOL) in a randomized, double-blind, placebo-controlled study of the effects of the inhaled corticosteroid fluticasone propionate (FP). A total of 342 patients with moderate asthma were treated twice daily for 12 weeks with FP powder (50, 100, or 250 micrograms) or placebo. At regular intervals, patients completed the Medical Outcomes Study Short Form-36, acute version (SF-36A), a general health status questionnaire measuring eight dimensions of HRQOL; the 20-item Living with Asthma (LWA-20) questionnaire, a disease-specific instrument measuring HRQOL; and three additional questions related to sleep loss and number of nighttime awakenings. Each of the three FP groups compared with placebo had significantly higher scores at study endpoint on the Physical Functioning (p < 0.001) and Role-Physical (p < or = 0.0001) dimensions of the SF-36A; the FP 100- or 250-micrograms groups compared with placebo also had significantly higher scores on General Health Perceptions (p < 0.03), Vitality (p < 0.007), and Mental Health (p < 0.02). At endpoint, all three FP groups compared with placebo had significantly better scores on the LWA questionnaire (p < 0.05) and on the sleep-related items (p < 0.0001). These data, collected using both a general health status questionnaire and an asthma-specific questionnaire, demonstrate that fluticasone propionate powder can improve HRQOL in patients with mild-to-moderate asthma.