This study examined the effect of fluticasone propionate aerosol on oral prednisone requirements in patients with severe asthma. Ninety-six patients dependent on oral prednisone were treated with placebo or fluticasone propionate aerosol (750 or 1000 &mgr;g twice daily) for 16 weeks. The dosage of oral prednisone was adjusted weekly according to predetermined criteria. Fluticasone propionate 750 and 1000 &mgr;g twice daily resulted in 69% and 88% of patients (low and high doses, respectively) not using any prednisone compared to 3% of placebo-treated patients by the end of the study. In the fluticasone propionate groups, forced expiratory volume in 1 s (FEV(1)) and peak expiratory flow rates and the number of nighttime awakenings improved at the last evaluable visit. In addition, the number of nighttime awakenings and symptomatic albuterol use declined relative to placebo values (p < 0.05). Fluticasone propionate aerosol was well tolerated. Fluticasone propionate aerosol (750 or 1000 &mgr;g twice daily) effectively and safely allowed most asthmatics who were dependent on oral corticosteriods to reduce or eliminate oral prednisone use while improving pulmonary function.