The ability of anti-T cell mAb therapy to prevent acute rejection of a tumor allograft was studied. Injection of both anti-CD4 and anti-CD8 rat Ig2b mAbs 1 day before intraperitoneal implantation of P815 tumor cells into AB6F1 mice prevented tumor rejection in most of the mice. However, injection of the same mAbs on day 8 of tumor growth, i.e., 2 days before the onset of tumor rejection, failed to prevent rapid elimination of P815 cells from the peritoneal cavity. Flow cytometric analysis revealed that whereas splenic T cells remained depleted in these mice for up to 6 days after mAb injection, peritoneal T cells returned to control levels in 4-6 days. Moreover, a significant number of rat IgG+ cells were found in the peritoneal cavity 2 days after mAb administration, thus demonstrating that T cells were not depleted but coated with the mAbs at that time. The antitumor activity of the mAb-coated T cells was not impaired, in that CD8+ peritoneal cells from mice rejecting allogeneic P815 tumor on day 10, and rat IgG+ peritoneal cells taken from mice 2 days after giving them anti-CD8 mAb on day 8, were similarly highly cytotoxic against P815 cells in vitro. Taken together, the results demonstrate that the failure of anti-T cell mAb therapy to prevent the acute rejection of allogeneic P815 tumor was associated with resistance of T cells at the site of rejection to the action of anti-T cell mAbs in vivo.