Ly-1 inducer T cells play a critical role in the regulation of antibody synthesis. One subset of Ly-1 T inducer cells (Qa-1-) can activate B lymphocytes to secrete IgM (1). A second (Qa-1 +) stimulates Ly-l,2 + T cells to differentiate into Ly-2 + T suppressor cells (1-3) that inactivate both subsets of inducer T cells, resulting in reduced levels of antibody formation and suppression.Recent reports (4-7) have indicated that T cells can also inhibit antibody responses without induction of Ly-2 T suppressors. Heterogeneous or cloned Ly-1 T cells failed to function as T helper (Th) 1 cells and inhibited primary IgM responses. This reflected direct inhibition of B cell maturation into IgM-secreting cells by the Ly-l:Qa-1 + fraction of inducer cells (4, 5). The nonhelper Ly-1 T cell induced B cell proliferation but inhibited primary IgM response to phosphorylcholine-ovalbumin (PC-OVA): suppression was I-A-restricted and required a hapten-carrier bridge between the B cell and the Ly-1 T cell clone (5). Inhibition of secondary responses with some nonhelper Ly-1 ÷ T cells (6, 7) has also been observed. In this case, T cell clones prevent an antigen-specific, major histocompatibility complex (MHC)-restricted interaction between carrier-specific Th cells and B cells.In the present study, we further analyzed the mechanism of inhibition of B cell responses in vitro, using Ly-1 T cell clones. We found that two Ly-1 T cell clones did not induce B cells to secrete antigen-specific IgG. Instead, these clones inhibited secretion of IgG antibody to T-dependent soluble antigens. Inactivation of the B cell occurred early and required cell-cell contact that is both I region restricted and antigen specific, resulting in an early proliferative response by antigen-specific memory B cells, without subsequent differentiation into antibody-secreting cells.