Human immunodeficiency virus (HIV) infection is associated with a profound impairment of T cell function. Hence, enhancement of T cell reactivity to viral and bacterial antigens is important in the treatment of patients with AIDS. To develop tools for amplifying T cell reactivity, we have immunized mice with human helper T cell clones and selected monoclonal antibodies (MAbs) that enhance in vitro blastogenic responses. MAb NDA5, which recognizes the leukocyte common antigen CD45, amplifies human T cell responses to mitogens and soluble antigens including HIV-1 glycoprotein (gp)-120 and peptides derived from the HIV-1 gp-120 sequence. In the presence of MAb NDA5, peripheral blood mononuclear cells (PBMC) from healthy, HIV-1-seronegative individual displayed augmented blastogenic responses to HIV-1 gp-120 and to HIV-1 gp-120 synthetic peptides. In vitro memory responses to various vaccines and to alloantigens were also enhanced in cultures with MAb. Similarly, the response of PBMC from AIDS patients to pokeweed mitogen, HIV-1 gp-120, and tetanus toxoid was enhanced with MAb NDA5. The finding that the in vitro immune response of patients with AIDS can be amplified with MAb NDA5, suggests that the in vivo immune response of immunodeficient individuals can also be enhanced.