Oral administration of 5 mg each of deuterium-labeled cortisol ([1,1,19,19,19-2H5]cortisol, cortisol-d5) and cortisone-d5 ([1,1,19,19,19-2H5]cortisone) to a human subject on two different occasions four weeks apart provided a useful means of characterizing the kinetics of the interconversion of cortisol and cortisone. From the data on plasma concentration measurements of cortisol-d5, cortisone-d5, cortisone-5, endogenous cortisol and endogenous cortisone by gas chromatography-mass spectrometry, it was demonstrated that (1) the plasma concentration ratio of cortisone-d5 to cortisol-d5 approached a plateau 4-5 h following either the cortisol-d5 or cortisone-d5 administration and the plateau values for the cortisone-d5 and cortisol-d5 administration were almost identical (about 0.43) and (2) dosing with only 5 mg of the deuterium-labeled steroids suppressed the plasma concentrations of endogenous cortisol and cortisone.