It has previously been demonstrated that within 6 hr after immunogenic stimulation the serum of mice contains a unique form of immunogenic antigen which represents complexes of Ig and antigen. The complexes are known to be strongly cytophilic for Ly2+ Ia+ FcR+ T cells and markedly enhance the IgG response. Anti-I-A treatment of mice suppresses the IgG antibody response and results in the generation of antigen specific T suppressor cells (Ts). Furthermore, anti-I-A treatment blocks the induction of the complexes and abolishes the enhancing effect the complexes exert on the IgG antibody response. The 6-hr cytophilic complexes were shown to block the function of Ts and allow a normal IgG response to take place; therefore, they act as mediators of a novel T-cell pathway called antisuppression. The blocking of the induction of the antisuppressor complexes by anti-I-A antibody was at least in part due to an effect on T cells. In conclusion, products of genes of the I-A subregion of the MHC control the activation early after immunization of a T-cell pathway which is called antisuppression since its major function is interference with the expression of suppression. Its early induction (within 6 hr) suggests that antisuppression may play a pivotal role in determining between immunity and unresponsiveness.