A maturation‐dependent change in phenotype and cytokine production from relatively immature CD161^– or CD161⁺, IL‐13⁺IL‐4⁺, IFN‐γ^–, to mature CD161⁺CD56⁺ IFN‐γ⁺ cells occurs in primary human α‐galactosyl ceramide‐reactive CD1d‐restricted natural killer T (NKT) cells under the control of IL‐12 and other monokines. Modulation of this process upon α‐galactosyl ceramide stimulation explains the opposite roles of NKT cells to drive type 1 and type 2 immune responses. Because the samedevelopmental changes occurred and were similarly regulated in T cells, the data establish that NKT cells should no longer be considered a functionally unique regulatory subset. However, the results of their analysis can be taken as a model for immunotherapeutic approaches with T cells for which a nominal or surrogate antigen is defined.