In the present study we have investigated the effect of CD45, CD45RA and CD45RO monoclonal antibodies (MoAbs) on the CD3 receptor-mediated proliferation of human T lymphocytes. It is shown that CD3-induced proliferation of purified resting T cells and quiescent T lymphoblasts (QTL) is promoted via all of the investigated CD45-associated epitopes. It is also shown that the CD45 molecules are required to be cross-linked for costimulation. The MoAbs enhance the interleukin-2 (IL-2) production of CD3-stimulated QTL. The elevation of the IL-2 production correlates with the increase in CD3-induced cell proliferation suggesting that the CD45-driven regulation of T lymphocyte activation is linked to the IL-2 pathway.