In recent years, much evidence has accumulated which demonstrates that an animal's immune system has the capacity to recognize its own antibody idiotypes. These findings suggest that self-idiotypic recognition may potentially play a role in the regulation of B-cell responses. The experiments presented in this report were carried out to determine if an animal develops the ability to specifically regulate the synthesis of antibodies specific for an antigen, subsequent to primary immunization to the particular antigen and concomitant with an initial antibody response. Employing the splenic fragment culture system we have compared the response of primary donor B cells in irradiated recipients which have been previously immunized to hemocyanin (Hy) alone or dinitrophenyl (DNP)-Hy plus Hy. The results indicated that only 25-30 percent of DNP- specific B cells stimulated by DNP-Hy in Hy immunized recipients could bestimulated by DNP-Hy in recipients immunized with Hy as well as DNP-Hy. B-cell responses to other haptens, such as fluoresceinated-Hy, and secondary DNP-specific B-cell responses were unaffected in DNP-Hy immunized animals. The nontrivial and specific nature of the observed decrease in primary DNP-specific B-cell responses was verified by the finding that the response of CB20 donor cells, which differ from BALB/c mice only in the immunoglobulin heavy chain allotype-linked locus, was unaffected in BALB/c recipient mice which had been immunized with DNP-Hy. Thus, it appeared that during a primary humoral immune response to a T- dependent antigen, an antibody-specific regulatory mechanism is induced which specifically limits the stimulation of hapten-specific primary, but not secondary, B cells. The important implications that these findings have for the understanding of the control of primary B-cell responses and the generation of secondary B cells is discussed.