Natural killer T (NKT) cells have recently been shown to play an important role in the rejection of malignant tumors and in the regulation of autoimmune diseases. Potent antitumor effects of the marine sponge-derived NKT cell ligand KRN7000 were observed in mice. Therefore, the elucidation of the natural ligand of NKT cells, which is currently still unknown, might have important clinical consequences for the treatment of cancer and autoimmune diseases. Analysis of cord blood mononuclear cells from healthy term infants demonstrated that in sharp contrast with the vast majority of cord blood lymphocytes, human NKT cells have already acquired a memory-activated phenotype before birth. This observation indicates that NKT cells encounter a natural ligand during fetal life and that this ligand is unlikely to be of microbial origin.