Dendritic cells (DC) play a critical role in initiating and directing adaptive immune responses against pathogens and tumours. Immature DC are thought to act as sentinels in peripheral tissues where their main function is to capture antigen at sites of infection, whereas mature DC are highly efficient at priming T-cell-mediated immune responses against infectious pathogens. The DC maturation process is thought to be an important step in the efficient generation of cytotoxic T lymphocytes (CTL). It is well established that many aspects of immune function, including CTL-mediated antiviral immunity, are modulated by neuroendocrine-derived products. Corticosterone (CORT), an adrenal hormone produced at increased concentrations during a stress response, has been shown to play a role in impaired CTL responses in stressed animals, leading to high mortality in mice normally resistant to viral infection. While direct effects of neuroendocrine mediators on CTL have been studied, little is known about their effects on DC that are critical for CTL priming. Here, we found that physiologically relevant concentrations of CORT, acting via the glucocorticoid receptor, functionally compromise DC maturation. DC exposed to CORT remained phenotypically and functionally immature after stimulation with lipopolysaccharide and were impaired for the production of interleukin (IL)-6, IL-12, and tumour necrosis factor-alpha. These effects were biologically significant, as CORT treatment resulted in a marked reduction in the ability of DC to prime naive CD8(+) T cells in vivo. These findings offer a potential mechanism underlying stress-associated immunosuppression.