We analyzed the ability of an allogeneic effect factor (AEF), produced using alloactivated A.SW (H-2s) responder T cells and irradiated A/WySN (H-2a) T cell-depleted stimulator spleen cells, to enhance the responsiveness of Lyb5+ and Lyb5- B cells to thymus-dependent (TD) and thymus-independent type 1 (TI-1) and type 2 (TI-2) antigens. We found that normal adult male CBA/CaHN (Lyb5+ + Lyb5-) B cells are activated by unfractionated AEF in primary in vitro IgM antibody responses to the SRBC (TD), TNP-LPS (TI-1), and TNP-Ficoll (TI-2) antigens. Adult male xid CBA/N (Lyb5-) B cells are activated by unfractionated AEF to respond to TNP-LPS but to neither SRBC nor TNP-Ficoll. Gel filtration of AEF on ACA 54 resolves several helper components. One component, which is I-Ak restricted in its activity and may represent a secreted form of an Ia antigen T cell receptor, interacts with histocompatible and functionally competent CBA/CaHN or CBA/N antigen-presenting cells to activate a primary anti-SRBC response of CBA/CaHN B cells but not of CBA/N B cells. A second antigen-nonspecific and H-2-nonrestricted AEF component, which consists of interleukin 2 and possibly also interleukin 1, activates anti-SRBC and anti-TNP-Ficoll responses of both CBA/CaHN B cells and CBA/N B cells. Such CBA/N B cell responses were potentiated by this AEF component only after its biochemical fractionation and only in the presence of a limiting number of T cells. These data indicate that both Lyb5+ and Lyb5- B cells are responsive to TD, TI-1, and TI-2 antigens in the presence of ancillary antigen-nonspecific help. They are also consistent with the notion that T helper cell activation of Lyb5+ B cells is H-2 nonrestricted and that T helper cell activation of Lyb5- B cells is H-2 restricted.