In patients with rheumatoid arthritis (RA) with a mean duration of six years, glucocorticoid receptor (GR) downregulation has been reported without change in cortisol levels. This phenomenon might play a role in the etiopathogenesis of RA. If this is the case, GR downregulation should also be found in early-diagnosed RA. We compared GR expression and cortisol levels of early RA patients with those of sex and age matched healthy controls. In early (disease duration less than one year) RA patients (52F/29M; mean [SE] age 63 +/- 2 years) and in 39 controls (23F/16M; mean age 63 +/- 2 years) blood samples were taken between 8:00 and 10:00 a.m. GR expression (GR number), cortisol levels (fluorescence polarization immunoassay, FPIA), ESR, CRP, and the presence of swollen and painful knees were determined. RA was diagnosed according to the ACR classification criteria. In early RA a significantly lower GR expression was found compared to controls. Interestingly, cortisol levels were also significantly lower. Both findings were due to the observed differences in the female population. In the male population no differences were found. No correlations were found among parameters of disease activity, nor was there a relation between GR expression and serum cortisol levels. In female patients with early-diagnosed RA a decrease in glucocorticoid receptor expression was found as well as a decrease in cortisol levels. Since normal glucocorticoid receptor expression was found in the male population with early-diagnosed RA, it remains questionable if glucocorticoid receptor expression is causally involved in pathogenesis of RA.