Monoclonal antibodies against the T cell differentiation antigen Lyt-1 were effective in the therapy of the murine Lewis lung carcinoma (3LL). A possible mechanism whereby anti Lyt-1 antibodies directly effect the tumor cells was unlikely because 3LL cells lack the Lyt-1 antigen. In addition, the curative effect of anti Lyt-1 antibodies was abrogated in mice depleted of T cells, supporting a mechanism whereby host Lyt-1+ cells were involved in tumor therapy. Treatment with anti Lyt-1 antibodies was not accompanied by depletion of Lyt-1+ cells from lymphoid organs, indicating that the administered antibodies altered Lyt-1+ cell functions without effecting their frequency. In view of the in vitro enhancing effects of anti Lyt-1 antibodies on responses, it is suggested that the potentiation of Lyt-1+ cell activity by passively administered anti Lyt-1 antibodies results in tumor rejection.