We previously reported that B lymphocytes obtained from BALB/c mice that had been immunized with M104E myeloma protein have an idiotype-specific enhancing activity for anti-dextran B1355S antibody responses in vivo. The enhancing cells were Thy-1-, Lyt-1-,2-, nylon wool-adherent and rabbit anti-mouse immunoglobulin (RAMG) dish adherent. The in vitro analysis described in this report also revealed that the enhancing cells had a B cell phenotype and were specifically enriched in M104E or J558 myeloma protein-coated dishes but not by irrelevant monoclonal antibodies. The significance of these B-B cell interactions were analyzed in vitro by using various Igh-1 and H-2 congeneic strains of mice. The idiotype immune B lymphocytes obtained from BALB/c and BAB-14 could enhance the antidextran antibody responses of BALB/c B lymphocytes in an idiotype-specific manner. On the other hand, C.AL-20 and CB-20 strains could not induce the idiotype-specific enhancing B cell activity in dextran-immune BALB/c B cells. These results suggest that the capability of enhancing B cell induction is related to the producibility of the respective idiotype in that strain of mice. Moreover, the B cells obtained from BALB/c mice immune to the idiotype cooperated well with the dextran-immune B cells of BALB/c but not of BALB.K and vice versa. These results indicate that successful cooperation between those two types of B lymphocytes requires the same MHC haplotype. The roles of these genetically restricted cellular interactions in the immune system are discussed.