In our previous paper, we demonstrated that anti-D44 MAb can, in the presence of complement, eliminate all the allocytotoxicity generated during a mixed lymphocyte reaction without affecting the alloproliferative response. As approximately 70% of CD4+ cells and 30% of CD8+ will be stained with anti-D44 MAb, we researched the functional role of the D44+ and D44- cells in each of these T cell subsets in the PWM-induced antibody response. We found that most of the helper activity for immunoglobulin (Ig) synthesis was mediated by CD4+ D44+ lymphocytes and that virtually all the suppressive activity was mediated by CD8+ D44- lymphocytes. Surprisingly enough, we noticed that the low level of Ig synthesis induced in B cells by CD4+ D44- lymphocytes could be strongly amplified by the addition of radiosensitive CD8+ lymphocytes, suggesting coexisting opposite immunoregulatory functions within the CD8+ T cell subset. These results, together with previous data, indicate that anti-D44 MAb subdivides T cells into subpopulations with distinct functional repertoires: a CD4+ D44+ helper subpopulation, a CD8+ D44+ cytotoxic subpopulation, and a CD8+ D44- suppressor subpopulation.