The priming of an appropriate anti‐tumor T cell response rarely results in the rejection of established tumors. The characteristics of tumors that allow them to evade a T cell‐mediated rejection are unknown for many tumors. We report on evidence that the expression of the immunosuppressive enzyme, indoleamine 2,3‐dioxygenase (IDO) by mononuclear cells that invade tumors and tumor‐draining lymph nodes, is 1 mechanism that may account for this observation. Lewis lung carcinoma (LLC) cells stimulated a more robust allogeneic T cell response in vitro in the presence of a competitive inhibitor of IDO, 1‐methyl tryptophan. When administered in vivo this inhibitor also resulted in delayed LLC tumor growth in syngeneic mice. Our study provides evidence for a novel mechanism whereby tumors evade rejection by the immune system, and suggests the possibility that inhibiting IDO may be developed as an anti‐cancer immunotherapeutic strategy. © 2002 Wiley‐Liss, Inc.