The capacity of (C57BL/6 × DBA/2)F1 mice to produce anti-(4-hydroxy-3-iodo-5-nitrophenyl)acetyl (NIP) IgE antibodies, as a result of immunization with 1 μg of NIP2-ovalbumin (OA) in the presence of Al(OH)3, was specifically suppressed by treatment of mice, either before or after immunization, with tolerogenic conjugates consisting of the hapten coupled to poly-N-vinylpyrrolidone (PVP) with an average mol. wt. of 10000. The suppression was hapten-specific, since it did not affect the immune response of the host to OA. The unresponsive state of the spleen cells of mice which had been tolerized with respect to NIP was maintained even after cell transfer into X-irradiated, syngeneic recipients and was shown to be due to hapten-specific suppressor cells. However, the splenic B cells of these mice did not possess any suppressive activity. The generation of an effective number of suppressor cells required between 1 and 2 days following the administration of the tolerogen. The suppressive effects observed on adoptive transfer could not be attributed to the carryover of the tolerogen, which might have been associated with the spleen cells of the donor mice, since the transfer of B cells of tolerized mice or of mice which had received 2 mg of the tolerogen 2-24 h before cell transfer did not abrogate the capacity of spleen cells of immune mice to mount an anti-NIP response. Hence, it may be concluded that NIP2-PVP induced, in addition to a probable receptor blockade of B cells, a central inhibitory mechanism which led to the development of an effective number of suppressor cells within 1 to 2 days after administration of NIP2-PVP.