In Jerne's network theory (1), the immune system is envisaged as a web of interactions between immunoglobulin variable domains. In this schema, regulation (amplification and suppression) of the immune response occurs when anti-idiotype antibody (Ab2) reacts with idiotypes (Ab 1) induced by foreign antigenic stimulation. Ab2 also induces and reacts with a nonspecific parallel set of antibody (Ab3)-bearing idiotypes shared with Abl but not binding the immunizing antigen. Induction, amplification, and suppression of the immune response thus result from the regulatory network of idiotype-anti-idiotype interactions.To probe the importance of idiotypic regulation on the heterogeneous response to the hapten 2,4-dinitrophenyl (DNP), 1 we have studied the expression of an idiotype (Id-460) associated with the DNP-binding, BALB/c IgA,~ myeloma protein MOPC 460 during in vivo anti-DNP antibody responses (2). Id-460 is expressed in a transiently dominant manner both in serum and by splenic anti-DNP plaque-forming cells; dominant expression occurs early in the secondary in vivo response to DNPovalbumin (OVA) in mice having Igh-V a and able to express light chains of the V~I group (2, 3). We have previously demonstrated (4-6) the existence of two helper T cells (Th) acting synergistically early in the course of in vivo secondary anti-DNP responses. One of these two Th was shown by adoptive transfer experiments to be lacking in T cells derived from mice treated from birth with anti-/~ antibody (7). This suggested the need for immunoglobulin (Ig) in the differentiation of this T cell. This cell was also shown to be Lyt-l+,2 -and antigen specific (8). We have proposed that this cell recognizes idiotype and is responsible for the dominant expression of Id-460 in the anti-DNP response. This is consistent with findings of Ig-recognizing T cells in other major idiotypic systems (9-11). However, in these other systems idiotype is associated with antibody directed against bacterial antigens. If inherited idiotypes are primarily directed at common environmental antigens and are important in resistance to common pathogens (12), the existence of an inherited, dominant idiotype associated