Budesonide is a highly potent non-halogenated glucocorticoid intended for the local treatment of lung disease. Budesonide is designed to have a high ratio between local and systemic effects. The biotransformation of 3H-budesonide was studied in vitro and compared to the biotransformation of 3H-triamcinolone acetonide and 3H-beclomethasone dipropionate. Budesonide was degraded 3--6 times as rapidly as triamcinolone acetonide in human and rat liver, respectively. Beclomethasone dipropionate was immediately hydrolyzed to the monopropionate in human liver. The degradation of beclomethasone monopropionate is the step that represents the major loss in biological activity and this step was only about one fourth as fast as the degradation of budesonide. 6 beta-hydroxy budesonide and 16 alpha-hydroxy prednisolone are two of the main metabolites of budesonide in human liver. The formation of these metabolites are important inactivation steps. The pharmacokinetics of 3H-budesonide was studied in healthy male volunteers after inhalation, oral and intravenous administration. The plasma half-life was 2.8 +/- 1.1 h (mean +/- SD), distribution volume 301.3 +/ 41.7 1 and plasma clearance 83.7 +/- 27.5 1/h. The systemic availability was 10.7 +/- 4.3% after oral administration and 72.8 +/- 42.0% after inhalation, corrected for the amounts of substance deposited in the inhalation device and oral cavity.