To examine the influence of avidity on the helper dependence of CD8+ T cells, purified CD8+ T cells from transgenic mice expressing a TCR specific for H-2Kb were tested for their responsiveness to spleen cells expressing different densities of H-2Kb. High avidity interactions resulted in the induction of strong proliferative responses by purified CD8+ T cells. These cells synthesized their own IL-2 and IL-2R. By contrast, low avidity interactions failed to induce proliferation or detectable IL-2 synthesis, although IL-2R were induced and addition of rIL-2 induced a proliferative response. These results are consistent with a model in which TCR avidity for Ag can determine the helper dependence of a CD8+ T cell.