Glucocorticoid receptor (GR) is expressed in the normal human adrenal gland, however, no study has been performed to evaluate the separate expression of alpha- and beta-isoforms (GRalpha and GRbeta) in normal human adrenals and in adrenocortical adenomas.GRalpha and GRbeta mRNA expression was examined by quantitative real-time PCR in 31 adrenal tissues including 19 non-functioning adenomas (NFA), 6 cortisol-producing adenomas (CPA) and 6 normal adrenocortical tissues. In addition, the presence and cellular localization of GRalpha and GRbeta proteins in adrenal tissues were studied by immunohistochemistry.Compared to normal adrenocortical tissues, both GRalpha and GRbeta mRNAs were significantly increased in CPA but not in NFA. Using anti-GRalpha antibody a strong nuclear staining was observed in NFA and CPA, and a less remarkable immunoreactivity was detected in some nuclei of normal adrenocortical cells. GRbeta immunostaining was absent in normal adrenal tissues and NFA, while a strong cytoplasmic and nuclear immunoreaction was found in CPA.Altered expression of GRalpha and GRbeta in CPA raises their possible role in the pathophysiology of these adrenal tumors, although further studies are needed to elucidate the potential significance of these findings.