The lymphocyte-specific receptors CD70 and CD27 appear to affect the lymphocyte function of all subsets on which they are expressed in a bidirectional way. The presence of CD70 on activated T and В cells as well as memory T and activated memory В cells and that of its ligand CD27 on all naive T cells (both resting and activated) as well as memory В cells, potentially allows crosstalk between all subsets involved in antigen-specific immune responses. How-ever. CD70 and CD27 appear to link not only the T helper response with respect to the CTLs and В effector cells. Though data on NK cells are limited expression of receptor and ligand on resting and activated subsets of these cells would allow additional crosstalk between the two types of killer effector cells (CTLs and NK cells) with respect to T cell help. The latter could contribute to the observed hierarchy ofCTL-medialed kill over that of NK cells in combatting virus infections, for example.The mounting evidence for the emerging synergy of the CD70 route with the CD28 and CD40 routes in vitro runs parallel with the first evidence for in vivo efficacy of manipulation of this route in tumor eradication and may herald new strategies for immunolherapeutic interventions for other diseases alone or in conjunction with CD28 and CD40.