In this paper we have examined the effects of i.v. administered monoclonal anti-I-J antibodies on tumor growth in syngeneic and semi-syngeneic hosts. These antibodies inhibit tumor growth in mice bearing the appropriate I-J-encoded gene product on their lymphoid cells at nanogram dosages. The spleens of monoclonal anti-I-J-treated primary tumor-bearing mice do not contain transferable tumor-specific cells. These findings suggest that inhibition of suppressor cell function may be the mechanism by which anti-I-J antibodies inhibit tumor growth. We have also demonstrated that tumors growing in F1 hybrid mice are inhibited by monoclonal anti-I-J antibodies reactive with either parental haplotype and that there is no evidence of synergy when both antibodies are administered simultaneously. This may indicate that I-J molecules are codominantly expressed on a critical component of the F1 suppressor pathway.