Inhaled glucocorticoids such as beclomethasone dipropionate, which are used in the treatment of asthma, may be associated with systemic adverse effects. To determine whether any systemic absorption following the inhalation of beclomethasone was a result of drug being absorbed from the lung (inhaled fraction) or the gastrointestinal tract (swallowed fraction), we studied normal subjects after the inhalation or swallowing of 2 mg beclomethasone dipropionate. Systemic activity was assessed using early morning cortisol suppression. Both inhaled and swallowed fractions produced significant systemic activity, the degree of which depended on the inhaler device used. Systemic activity was greater using a dry powder inhaler (52%) than using a metered dose inhaler with a large volume spacer (28%). These findings suggest that to limit potential adverse effects from high-dose beclomethasone dipropionate it is better to use a metered dose aerosol with large volume spacer than a dry powder.