Monoclonal antibodies (mAb) NDA3 and NDA4 were generated by hyperimmunizing mice with an alloreactive human T cell clone and fusing the splenocytes with the NS1 myeloma. Immunofluorescence studies indicated that these mAb react with activated, but not with resting T and B lymphocytes or with other types of cells. Immunoprecipitation studies with 125-I-labeled extracts from T and B cell lines demonstrated that the m.w. of the antigen recognized by mAb NDA3 is 36,000 and that of NDA4 is 46,000. Studies on the effect of mAb NDA3 and NDA4 on Epstein Barr Virus-transformed lymphoblastoid B cell lines (LBCL) demonstrated that these antibodies stimulate B cell proliferation and Ig synthesis. The level of expression of NDA3 and NDA4 on the membrane of LBCL is significantly augmented when cells are grown in the presence of recombinant human interferon-beta and gamma and is decreased in the presence of 12-O-tetradecanoyl-phorbol-13-acetate. These observations, in conjunction with the stimulatory effect of mAb NDA3 and NDA4 on the growth and differentiation of LBCL, suggest that these new differentiation antigens, NDA3 and NDA4, may serve as growth factor receptors.