Glucocorticoid receptors (GR) are ubiquitous molecules and are present also in the hippocampus and in several other nervous and immune tissues. Peripheral blood mononuclear cells (PBMCs) are a good model for studies of GR in humans. Glucocorticoids are important for maintaining cellular and humoral homeostasis and are key mediators of neuroendocrine-immune regulatory interactions. The increase of cortisol is immunosuppressive and reduces GR concentration both in nervous and immune systems. Variation of glucocorticoids in healthy aged subjects and athletes has been shown. Prompted by these results, we have investigated in man a possible relationship between GR binding capacity in the PBMCs and age, in relation also to plasma testosterone and cortisol. The same parameters have been examined in a group of soccer players for comparison with the sedentary group. GR binding capacity was higher in younger subjects than in older ones, and lower in the group of athletes than in the younger and older sedentary subjects. In the sedentary group a negative correlation was present between GR binding capacity and age. Plasma cortisol was higher and testosterone lower in the athletes; they were negatively correlated in athletes and positively correlated in the sedentary subjects. The results for athletes agree with their lower anabolic/catabolic balance. The mechanism of reduced GR levels in relation to age and sport activity could involve a loss or an involution of receptor synthesis. However other possibilities, such as altered distribution of lymphocyte subpopulations with different receptor concentrations and with different cytokine production, cannot be excluded. Several neuroendocrine-immune interactions could be responsible for reduced GR levels with age and sport activity in man.