11beta-Hydroxysteroid dehydrogenase type 1 and type 2 (11betaHSD1 and 11betaHSD2) isozymes catalize the conversion of inactive glucocorticoids (e.g. cortisone) to their active forms (e.g. cortisol) and vice versa, respectively. Reverse transcription-polymerase chain reaction allowed the detection of 11betaHSD1 and 11betaHSD2 mRNAs in the human adrenal cortex, liver, kidneys, as well as in six aldosterone-secreting adenomas. 11betaHSD1 and 11betaHSD2 activity, as evaluated by the capacity of the microsomal fraction to convert [3H]cortisone to [3H]cortisol and vice versa, was detected in both human adrenal cortex and aldosteronomas, although it was less elevated than in liver and kidneys. Aldosteronomas possessed more intense 11betaHSD1 activity and less intense 11betaHSD2 activity than the normal adrenal cortex. The hypothesis is advanced that the elevated local concentration of steroid-hormone intermediates occurring in aldosteronomas up-regulates 11betaHSD1 and down-regulates 11betaHSD2, thereby contributing to their enhanced steroidogenic function.