Recent findings suggest an important role of subtle changes in the plasma levels of inflammatory cytokines within the brain-immune interplay. It is unclear how such changes are regulated in the absence of acute inflammatory or infectious stimuli. Endocrine systems are a good candidate, because innate immunity and the hypothalamo-pituitary-adrenal (HPA)-system are closely related: glucocorticoids have immunosuppressive properties and modulate cytokine release from stimulated mononuclear blood cells in vitro and the immune response in vivo, but it still remains unclear, whether they also modulate circulating cytokine levels in the absence of immunological stimuli. We measured the influence of 1.5 or 3.0 mg dexamethasone (DEX) per os at 09:00 or 21:00 hours on body temperature, cortisol plasma levels, differential white blood cell counts, and cytokine plasma levels in 40 healthy male volunteers using a double-blind, placebo-controlled study design. In addition to significant morning-evening differences in tympanic temperature and several immune parameters, we found that DEX-intake significantly increased tympanic temperature, decreased cortisol plasma levels, altered differential white blood cell counts and induced changes in unstimulated plasma cytokine levels. Whereas the levels of TNF-alpha and sTNF-R p75 were reduced, the levels of sTNF-R p55 increased after a transient decrease.