The influence of various cyclodextrins(CyDs) on the stability of hydrocortisone butyrate was investigated in aqueous solution by high performance liquid chromatography. At constant pH and temperature the decomposition of HB followed an apparent first order process. A maximum stability was obtained near the pH 4.0. In the neutral pH region the steroid decomposed stepwise, the 17-butyrate (HB) migrating to form hydrocortisone-21-butyrate which was hydrolyzed to give hydrocortisone and then decomposed into unidentified compounds. To elucidate the stabilization modes of HB by CyDs, the effects of pH, ionic strength, solvent, temperature and CyD concentration on the isomerization rate of HB were studied in the absence and presence of CyDs. Furthermore, activation energies and apparent stability constants were determined. The stability of HB was improved by the inclusion complexation with α-, y- and 2, 6-dimethyl-β-cyclodextrins(DM-β-CyD), whereas the rearrangement of HB was somewhat accelerated by β-CyD complexation in neutral and alkaline region above pH 5.0. It was concluded that the inclusion complexation of HB with y-CyD, especially, DM-β-CyD may be a potentially useful means of increasing the stabiof the steroid.