Human Vα24 NKT cells bearing an invariant Vα24JαQ antigen receptor, the counterpart of murine Vα14 NKT cells, are activated by a specific ligand, α-GalCer, in a CD1d-dependent manner. Here, we demonstrate decreased numbers of circulating Vα24 NKT cells in patients with primary lung cancer compared to healthy volunteers. However, Vα24 NKT cells and DCs from lung cancer patients were functionally normal, even in the presence of tumor. Furthermore, levels of Vα24 NKT cells in surgically resected lung tissue appeared to be equivalent to those of Vα14 NKT cells in the mouse lung. Levels of Vα24 NKT cells in the tumor tissue itself were increased about 2.5 times. Administration of α-GalCer-pulsed DCs expanded Vα14 NKT cells in the lung more than 10 times, and the increased levels were sustained for 1 week. This may explain the previous finding that α-GalCer-pulsed DCs exerted strong antitumor activity in mouse lung tumor metastatic models. The potential use of α-GalCer-pulsed DCs for immunotherapy aimed at activating endogenous Vα24 NKT cells in the lung of cancer patients is discussed. © 2002 Wiley-Liss, Inc.