The role of natural killer T (NKT) cells in the immune response to tumor cells has been largely unexplored. As a model of adoptive tumor immunotherapy, cells from the draining lymph nodes of mice immunized with a tumor-specific or irrelevant antigen were transferred to naı¨ve recipients with established tumor. Inhibition of early tumor growth (day 4) required the transfer of both CD8 and Ja18 (NKT) cells from immunized animals without regard to immunogen. In contrast, CD8 cells, but not Ja18 cells, were necessary for the inhibition of late tumor growth (day 8). Thus, the developing tumor changes in sensitivity to NKT-mediated events and the role for NKT cells cannot be replaced by the presence of tumor-specific cells during early tumor growth. This suggests that recruitment/activation of Ja18 NKT cells is an important consideration during the immune therapy of early stage tumors.