We have previously demonstrated dose-dependent nocturnal cortisol suppression by inhaled beclomethasone and budesonide in asthmatic children. This has now been confirmed in a controlled study. Eighteen healthy adults inhaled either a single evening dose of 400 micrograms budesonide or placebo or 400 micrograms budesonide twice daily for 2 wk. Overnight blood samplings for cortisol and adrenocorticotropic hormone were taken at the beginning of the trial, at the end of the treatment period, and after stopping the medications. Compared with placebo, the nocturnal cortisol production was significantly reduced by 40% after a single dose of budesonide (p = 0.020) and by 37% after 2 wk of budesonide (p = 0.045). These data indicate that there is a single-dose rather than a cumulative suppressive effect of inhaled corticosteroids using the specific dose and regimen studied in this protocol. The effect is not related to the underlying problem, namely asthma. The clinical relevance of these findings can only be elucidated in long-term follow-up studies. We believe that our findings explain the recent identification of abnormalities in bone turnover on inhaled corticosteroids in the absence of other systemic effects. The findings emphasize the need for a cautious step-wise approach to asthma therapy.