Allogeneic mouse spleen cells of strong hlstocompatibility difference mixed in vitro at equal proportions are unable to make a primary antibody response against thymus‐dependent as well as thymus‐independent antigens. This non‐responsiveness is not due to mutual cytotoxicity, because the reactivity of the cell partners can be recovered if the mixtures are transferred to irradiated hosts isoimmune to one of the cell partners. Responsiveness of allogeneic cell mixtures depends on the proportions at which the allogeneic cells are mixed, the strength of histocompatibility differences, the functional state of the ad mixed cells, the timing of the admixture, and the T/B cell ratio of the ad mixed cells. Supernatants from cultured allogeneic spleen cell mixtures can restore responsiveness of otherwise non‐responsive B‐spleen cells. The results suggest that interaction between cultured allogeneic T‐cells leads to rapid formation of soluble material which, depending on concentration, can either initiate or inhibit the maturation of B‐cells into antibody‐secreting cells in the presence of s