ACKGROUND--Systemic absorption of inhaled corticosteroids may adversely influence the function of the hypothalamo-pituitary-adrenal axis, bone metabolism, and circulating leucocytes. These changes can be used to assess the safety of different types and modes of administration of these drugs. METHODS--The study was a randomised, double dummy, crossover design with nine healthy adults. It compared the effects of beclomethasone dipropionate and budesonide (given by metered dose aerosols with and without their respective large volume spacers (Volumatic and Nebuhaler) attached) on serum cortisol, 24 hour urinary free cortisol, and plasma osteocalcin concentrations, and circulating neutrophils and lymphocytes. Subjects inhaled the drug (1 mg) and matching placebo at 0900 and 2200 hours on each of six study days. Blood samples were taken hourly for six hours after the morning dose and at the end of the study period. RESULTS--All results were within the reference ranges. Both drugs caused similar reductions in serum cortisol four to six hours after inhalation. These changes were not affected by the use of a large spacer and did not persist at 24 hours. Use of spacers tended to increase the haematological effects of the steroids. Beclomethasone dipropionate inhaled through a Volumatic provoked a rise in circulating neutrophils compared with placebo although lymphocyte numbers were unaffected. Budesonide did not influence neutrophil numbers but did reduce circulating lymphocytes, numbers of which were further reduced when the Nebuhaler was used. There were no significant changes in plasma osteocalcin concentration or 24 hour urinary free cortisol excretion with budesonide, with or without a spacer. Beclomethasone dipropionate inhaled without a spacer reduced urinary cortisol and plasma osteocalcin at 24 hours; however, use of the Volumatic protected against these effects. CONCLUSIONS--Attaching a Volumatic reduces the systemic effects of 2 mg aerosol beclomethasone dipropionate on the hypothalamo-pituitary-adrenal axis and circulating osteocalcin concentrations. This study did not establish whether the Nebuhaler reduces the systemic effects of budesonide. When large spacers are used, 2 mg per day of beclomethasone dipropionate and budesonide seem to be equivalent in terms of unwanted effects.