CD6, a 100 kD monomeric T cell surface glycoprotein, is a member of the scavenger receptor cysteine-rich protein superfamily. It is expressed on mouse thymocytes and splenic T cells and neurons, but not on splenic B cells. CD6 has a long cytoplasmic tail in mice, with two proline-rich domains that interact with the –SH3 domain binding sequence. CD6 binding to its ligand, CD166 (ALCAM), serves as a costimulatory molecule through its interaction with SLP-76. CD6 mediated signaling may contribute to thymocyte survival and functional avidity in mice and men.