Study objectives: To compare the effect of 4 weeks of treatment with fluticasone propionate (FP), 100 μg bid, delivered either via the Diskhaler (GlaxoSmithKline; Middlesex, UK) or a hydrofluoroalkane (HFA)-134a pressurized metered-dose inhaler (pMDI) on airway responsiveness. Design: A single-center, randomized, double-blind, double-dummy, placebo-controlled crossover study. Setting: Outpatients. Patients: Patients with mild asthma who had not received corticosteroids for 4 weeks prior to the study. Interventions: FP, 100 μg bid, via the Diskhaler, HFA-134a pMDI, or placebo for periods of 4 weeks. Measurements and results: The primary efficacy variable was the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) at the end of each 4-week treatment period. The FP formulations were defined as equivalent if the treatment difference was within ± 1 doubling dose of methacholine. Forty-seven patients were included in the per-protocol population. The baseline PD20 geometric mean was 0.21 mg, which increased to 0.55 mg with FP via the HFA-134a pMDI and to 0.68 mg with FP via the Diskhaler. The treatment difference between adjusted means was - 0.16 doubling doses (95% confidence interval, - 0.62 to 0.31 doubling doses; p = 0.503). Both significantly decreased airway responsiveness compared to placebo (p <0.001), and also significantly increased lung function with no difference between the two active groups. FP was well tolerated with few adverse events and no effect on serum cortisol levels. Conclusions: FP delivered via the HFA-134a pMDI is equivalent to FP via the Diskhaler in reducing airway responsiveness.