CD137 (ILA/4–1BB) is a member of the tumor necrosis factor receptor family, expressed on activated T lymphocytes. The expression of CD137 is strictly activation dependent in primary cells. Co-stimulation through CD137 enhances T lymphocyte activation and may enable rejection of tumors in vivo. The gene for human CD137 resides on chromosome 1q36, in a cluster of related genes, and this chromosomal region is associated with mutations in several malignancies. Bidirectional signalling has been demonstrated for the CD137 receptor/ ligand system. While cross-linking of CD137 activates T lymphocytes, cross-linking of the CD137 ligand has the opposite effect. This reverse signalling through the CD137 ligand inhibits proliferation of T lymphocytes and induces programmed cell death. Soluble forms of members of the TNF receptor family have been demonstrated for the various members. The soluble isoforms of CD137, sCD137, are generated by differential splicing and can be detected at enhanced concentrations in sera of patients suffering from various diseases. The expression of CD137 isoforms in lymphocytes has been shown and association of sCD137 with activation-induced cell death demonstrated. The levels of sCD137 released by activated lymphocytes have been reported to reflect a negative feed-back control of inflammation in some autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis.