The extracts of thymocytes and spleen cells of mice that had been primed with a carrier antigen (keyhole limpet hemocyanin, KLH) were found to augment the in vitro secondary antibody response of spleen cells against a hapten (2,4-dinitrophenyl, DNP) coupled to KLH, when they were added to the culture 1 to 3 days after the start of cultivation. The factor that augments the antibody response (TaF) had similar physicochemical properties to those of the previously reported antigen-specific suppressive T cell factor (TsF) and was removed by absorption with the immunoadsorbent composed of only relevant antigen (KLH) but not of anti-immunoglobulin antibodies. TaF and TsF were, however, distinguishable by differential absorption with various alloantisera directed at different subregions of the H-2 histocompatibility complex. The activity of TaF was removed by antisera reactive to the products of the I-A subregion, being distinct from TsF which was absorbed by those specific for the I-J subregion. Evidence was presented that the I-region determinants on TaF are distinct from those on Ia antigens that are primarily detectable on B cells, suggesting that TaF is determined by a different locus (Ia-6 ?) from that for B cell Ia antigen (Ia-1). Furthermore, it was shown that TaF is a product of Lyt-1+, 2-, 3- T cells, a fact which clearly distinguishes the cellular origin of TaF from that of TsF which is Lyt-1-, 2+, 3+. TaF can enhance the antibody response only if the helper T cell having the same carrier-specificity was present in the culture, indicating that TaF is not a helper T cell-replacing factor. The presence of both suppressive and augmenting T cell factors determined by different I subregions in the extract of primed lymphoid cells suggests that the balance of these T cell factors determines the magnitude of the antibody response.