Human lymphocytes primed in vitro by allogeneic cells develop lymphocyte populations with different functions. Cells with a memory of the allogeneic contact and cytotoxic effectors have been identified previously. We now report on a third lymphocyte population generated by repeated in vitro sensitization. This is of suppressor lymphocytes that can inhibit the primary proliferation of unsensitized lymphocytes. Our experiments indicate that these human suppressor cells are most probably T lymphocytes, adherent to glass or nylon wool, and radioresistant. They derive from both the large blast cells and the small, nondividing lymphocytes that are observed on day 7 of the allogeneic response. The suppressor cells release suppressor factor(s) upon restimulation. Studies on the specificity of the suppression have shown that suppressor cells are specific to the HLA-DR antigens presented by stimulator lymphocytes and that they probably release the suppressor factor only when confronted with the specific HLA-DR antigen. However, when the suppressor factor is produced, the proliferative response to any stimulating cell is inhibited regardless of its HLA-DR antigens. On the other hand, the suppressor factor can only suppress the proliferation of lymphocytes from some individuals. This restriction suggests that suppression can only occur when the producer of the suppressor factor and the responding lymphocytes that are being tested, have some identities in common. No evidence in favor of an HLA-D restriction has been obtained so far.