cDNA library subtraction techniques were used to identify transcripts expressed by activated mouse αβPTCR⁺ CD4⁻CD8⁻ (double-negative; DN) T cells, a subset of natural killer T (NKT) cells. The most frequent cDNAs identified included the chemokines TCA3, macrophage inflammatory protein-1α (MIP-1α), MIP-1β, and lymphotactin (LPTN), the cytokines interleukin-4 (IL-4) and interferon-γ (IFN-γ), and a granzyme. We also identified a new member of the immunoglobulin superfamily (Ig-SF). This molecule was designated class I-restricted T cell-associated molecule (CRTAM) as a result of its restricted expression pattern in T cells. Human CRTAM was also identified, and shares the same expression pattern as the mouse molecule. LPTN and CRTAM exhibit the same expression pattern in T cells, suggesting the existence of a gene expression program common to class I-MHC-restricted T cells. J. Leukoc. Biol. 67: 725–734; 2000.