We show here that the interaction of a radiation leukemia virus-induced thymoma, C6VL, with its cognate retroviruses occurs in the vicinity of the T cell receptor (TCR). While an anti-clonotypic antibody completely inhibits this interaction, antibodies specific for another T cell receptor complex determinant, L3T4, only partially inhibit the cell-retrovirus interaction. Several antibodies to more abundant cell-surface determinants (T200, Ly15, H-2Db) do not inhibit this interaction. Under capping conditions, either of the antibodies to L3T4 or TCR epitopes modulate virus binding receptors from the surface of C6VL/1 cells. L3T4 and the TCR do not comodulate significantly on the surface of C6VL/1 cells. These experimental findings implicate the existence of rare TCR-L3T4 complexes on C6VL/1 cells, and the involvement of these complexes in the binding of C6VL/1 to its cognate retrovirus. In addition, the clonotypic anti-TCR antibody inhibits C6VL/1 cell proliferation at concentrations that block its binding to its produced retroviruses.