NDA4, a cell surface protein of molecular mass 46 kDa common to activated peripheral blood B and T cells, plays a unique role in the control of B and T cell maturation. NDA4 inhibits B and T cell activation, as mitogen-stimulated B and T cell blastogenic responses are decreased in the presence of mAb NDA4, the antibody recognizing NDA4. After mitogen-activation, however, the regulatory function of NDA4 changes. Addition of mAb NDA4 to cultures of Staphylococcus aureus Cowan strain A-activated B cells or alloreactive T cell clones stimulates their proliferation. NDA4 epitopes are conserved across primate species lines and are present on transformed cells of neuroectodermal origin. NDA4 is synthesized as a molecular mass 50 kDa precursor and is processed to a mature 46 kDa form within 30 min. The NDA4 Ag also exists as soluble forms of 40 and 42 kDa. The membrane and soluble forms of NDA4 have been purified to homogeneity and sequenced by N-terminal Edman degradation.