The aim of this study was to compare the effect of 7 days nebulised fluticasone propionate (FP) with oral prednisolone on 24-h urinary-free cortisol excretion, systemic exposure and safety. This was a randomised, double-blind, double-dummy, two-way crossover study. Thirty-one children (19 male, 12 female, mean age 8 years) with stable asthma were randomly assigned to 7 days treatment with either FP Nebules (2 x 0.5 mg/2 ml bd) or prednisolone tablets once daily (2 mg/kg/day for 4 days [maximum 40 mg] followed by 1 mg/kg/day or half the original dose for 3 days [maximum 20 mg]). After a 2-4 week washout period, patients received the second treatment for 7 days, followed by a 2-week follow-up visit. The primary outcome measure was 24-h urinary-free cortisol concentrations corrected for creatinine. Nebulised FP (1 mg bd) had significantly less effect on 24-h urinary-free cortisol excretion than oral prednisolone (8.9 ng/ml for FP and 5.0 ng/ml for prednisolone, P = 0.001). Systemic exposure to FP was also low. In conclusion, FP Nebules had significantly less effect on hypothalamic-pituitary-adrenal axis function than oral prednisolone in asthmatic children when used at doses recommended for the treatment of an acute exacerbation of asthma.