Alternative splicing of the human glucocorticoid receptor (GR) primary transcript generates two protein isoforms: GR-alpha and GR-beta. We investigated the expression of both GR isoforms in healthy human cells and tissues. GR-alpha mRNA abundance (x10(6) cDNA copies/microg total RNA) was as follows: brain (3.83 +/- 0.80) > skeletal muscle > macrophages > lung > kidney > liver > heart > eosinophils > peripheral blood mononuclear cells (PBMCs) > nasal mucosa > neutrophils > colon (0.33 +/- 0.04). GR-beta mRNA was much less expressed than GR-alpha mRNA. Its abundance (x10(3) cDNA copies/microg total RNA) was as follows: eosinophils (1.55 +/- 0.58) > PBMCs > liver > or = skeletal muscle > kidney > macrophages > lung > neutrophils > brain > or = nasal mucosa > heart (0.15 +/- 0.08). GR-beta mRNA was not found in colon. While GR-alpha protein was detected in all cells and tissues, GR-beta was not detected in any specimen. Our results suggest that, in physiological conditions, the default splicing pathway is the one leading to GR-alpha. The alternative splicing event leading to GR-beta is minimally activated.