Immunoregulatory antigen-presenting cells (APC) play an important role in maintaining T cell homeostasis and self-tolerance. In particular, recent evidence demonstrates a role for inhibition of T cell proliferation by macrophage tryptophan catabolism involving the activity of the enzyme indoleamine 2,3-dioxygenase (IDO). Dendritic cells (DC) have also been shown to exert immunoregulatory effects mediated by tryptophan catabolism and to cause T cell apoptosis. In the present study, we have comparatively analyzed the expression of IDO activity by murine macrophages and splenic DC. By means of PCR, Western blotting and measurements of enzyme functional activity, we obtained evidence that, different from macrophages, DC constitutively express IDO. Following activation by IFN-gamma, the latter cells, in particular the CD8 alpha(+) subset, exhibit high functional activity and, unlike macrophages, mediate apoptosis of T(h) cells in vitro. Therefore, in the mouse, CD8 alpha(+) DC may be unique APC capable of fully expressing the IDO mechanism functionally.