OKT3 monoclonal antibody recognizes surface antigenic structures present on all human mature T lymphocytes and is mitogenic for resting peripheral T cells. Recent reports suggest that these structures are linked to the specific antigen receptor of the T cells and play an important role in T-cell activation. We have tested the mitogenic action of OKT3 on resting lymphocytes from human newborns, their mothers, and unrelated adults. We found that the proliferative response of cord T cells to OKT3 is significantly lower than the response of maternal and adult cells at all doses of the antibody tested (5-1000 ng/ml). This difference was not dependent on culture conditions (source of serum, kinetics induced by the OKT3 antibody, or different proportions of adherent cells in peripheral blood mononuclear leukocytes), and could only to some extent be accounted for by differences in the proportions of OKT3-binding cells between these populations. Removal of adherent monocytes largely diminished the OKT3-induced proliferation of maternal and adult cells, by an average of 70-80%. In contrast, it significantly enhanced the proliferation of cord cells. The proliferative response of cord T lymphocytes to the two polyclonal T-cell activators phytohaemagglutinin and concanavalin A was similar to or greater than that of mothers and other adults.