Spontaneous rejection of syngeneic intraocular P91 mastocytoma occurred by a T cell-dependent immune process that produced extensive, irreparable damage to normal ocular tissues indicative of a delayed-type hypersensitivity (DTH) lesion. We investigated the contribution of other effector modalities in this tumor resolution. Antibody was not responsible for either tumor rejection or phthisis of the tumor-containing eye since passively transferred hyperimmune serum failed to produce either tumor rejection or the characteristic ocular lesions. Moreover, the destructive pattern of tumor rejection occurred in splenectomized hosts which had depressed anti-P91 serum antibody and in a congenic strain (B10-.D2oSn) lacking the C5 complement component. The likelihood that tumor necrosis factor (TNF) was involved in this pathogenesis was also ruled out by the observation that P91 tumor cells were not susceptible to lysis by recombinant TNF. A different pattern of tumor resolution was observed when the opposite eye was challenged with tumor. In this case, the tumor was rejected without damaging any major ocular structures. Histological analysis demonstrated a mononuclear cellular infiltrate which was identified by immuno-histology to be Thy 1+, Lyt 2+. Thus, although both forms of cell-mediated immunity are available to the host, only one predominated in each eye. These results suggest that unique immuno-logical control mechanisms influence the outcome of tumor resolution in the eye.