CD70 is a surface Ag found on activated but not resting T and B lymphocytes. The biologic activity of this Ab-defined cell surface molecule on lymphocytes has not been established. Therefore, in an effort to understand the function of the CD70 protein, a mAb defining the CD70 Ag was used to isolate by expression cloning the cDNA responsible for the CD70 molecule. The predicted protein product is a type II transmembrane protein. Bioassays demonstrated that the CD70 cDNA clone expressed in African green monkey kidney cells would induce the proliferation of PHA-costimulated T cells. Comparison with known sequences indicates identity with the CD27 ligand. Therefore the molecule defining the CD70 Ag is identical to the recently defined ligand for CD27.