Corticosteroids are the foundation of pharmacologic treatment for children with asthma. However, high-dose inhaled corticosteroid treatment can cause hypothalamic-pituitary-adrenal (HPA) axis suppression. We investigated the effect of three doses of mometasone furoate administered via dry-powder inhaler (MF-DPI) on the HPA axis in children. Fifty children (6-11 years) with mild asthma of > or =6 months' duration were randomized to MF-DPI, 100 (n = 13), 200 (n = 13), or 400 micrograms b.i.d. (n = 12), or placebo (n = 12) for 29 days. The primary end point was change from baseline in the 12-hour area under the plasma-cortisol-concentration-time curve (AUC). Secondary parameters included plasma cortisol response to cosyntropin stimulation and 24-hour urinary free cortisol concentrations. Compared with placebo, AUC changes associated with treatments of MF-DPI, 100 or 200 micrograms b.i.d., were not significant, whereas a significant change was observed with MF-DPI, 400 micrograms b.i.d. (27%; p = 0.05). Responses to cosyntropin stimulation and urinary cortisol measurements were similar to placebo with all MF-DPI doses. All regimens were well tolerated. MF-DPI did not have a significant effect on plasma or urinary cortisol levels at doses up to 200 micrograms b.i.d. in children with mild asthma. Higher MF-DPI doses may potentially suppress the HPA axis.