The cytotoxic T cell is thought to be a primary effector of allograft rejection. In vitro studies have demonstrated that the interaction between cytotoxic T cells and target cells involves cell surface adhesion molecules that result in conjugate formation, with subsequent antigen recognition, T cell activation, and target cell lysis. Experiments have also demonstrated the ability of monoclonal antibodies with specificity for two human T cell adhesion molecules, lymphocyte function associated (LFA) antigen-1 (LFA-1, CDlla,<[beta]-chain/CD18,[beta]-chain) and LFA-2 (CD2), to inhibit conjugate formation in vitro. Studies in a nonhuman primate model were undertaken to determine whether the in vivo administration of monoclonal antibodies with specificity for the alpha chain of LFA-1 (CD11a) or with specificity for CD2could modulate in vivo T cell function. Cynomolgus monkeys (Macaca faacicularis) received 10 daily intravenous infusions of either anti-CD11a, anti-CD2 or both anti-CD11a and anti-CD2 monoclonal antibodies. Antibody administration was well tolerated and resulted in high levels of circulating murine monoclonal antibody in the peripheral circulation. Nearly all the animals generated antimurine antibodies that were specific for both idiotypic and nonidiotypic determinants of the infused mouse protein. Circulating lymphocytes and T cells were not depleted by treatment with anti-CD11a or anti-CD2 mAbs; in fact, treatment with the combination of anti-CD11a plus anti-CD2 or anti-CD11a alone led to increased numbers of circulating lymphocytes and T cells. Modulation of the LFA-1 molecule on circulating T cells occurred as a result of treatment with anti-CD11a (or the combination of anti-CD11a plus anti-CD2), whereas treatment with anti-CD2 (or anti-CD11a plus anti-CD2) did not result in modulation of the CD2 antigen despite detectable levels of circulating anti-CD2 mAb. In vivo T cell function was assessed by placement of skin allografts. As compared with treatment with saline or a control mAb, allograft survival was significantly prolonged in animals treated with