1. The aim of this study was to compare the systemic bioactivity of low and high doses of inhaled budesonide and fluticasone propionate given by respective dry powder inhaler devices. 2. A randomised, single blind cross-over design was used in nine healthy subjects who were given 800 micrograms day-1 of budesonide Turbohaler (B800) for 1 week, followed by 1 week of 1600 micrograms day-1 (B1600), or fluticasone Diskhaler 750 micrograms day-1 (F750) for 1 week followed by 1 week of 1500 micrograms day-1 (F1500). There was a 1 week washout between treatments with fluticasone or budesonide. A twice daily dosing regime was used and mouth-rinsing was employed to reduce gut bioavailability as well as to obviate local adverse effects. 3. Parameters of hypothalmic-pituitary adrenal (HPA) axis activity and bone metabolism were measured at baseline (B0/F0), at the end of each week of treatment and after the 1 week washout (F0 or B0). 4. Both fluticasone and budesonide significantly (P < 0.05) attenuated the post tetracosactrin serum cortisol at low and high doses whilst early morning cortisol was unchanged. No dose-response effect was observed with either drug, and there was no significant difference between treatment with fluticasone or budesonide. 5. Neither budesonide nor fluticasone produced significant suppression of plasma osteocalcin, although the higher doses of both drugs significantly reduced fasting urinary calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)