AbstractCultures of T cell‐depleted mouse spleen cells (B cells) were reconstituted with either allogeneic or syngeneic untreated T cells. The primary (day 4) antibody‐forming cell responses to sheep red blood cells were then compared. In almost all combinations and regardless the nature of the H‐2 incompatibility between the T and B cells tested, small numbers of untreated allogeneic T cells provided better help [positive allogeneic effect (AE)] than the same numbers of syngeneic T cells; only in the combination in which B10.A(2R) T cells were added to B10.A(4R) B cells (differing at I‐B, I‐J, and S), no AE at all appeared. A strong positive AE was induced when the incompatibility included or consisted of I‐A. A strong positive AE was also induced across an I‐E difference, provided the B cells expressed the Eαmolecule on the cell surface and did not differ at K/D. A negative AE only occurred when the H‐2 incompatibility on the B cells included or consisted of a difference at the K and/or D locus.In contrast to untreated T cells, anti‐Lyt‐1 plus complement‐treated T cells induced neither a positive nor a negative AE. T cells treated with anti‐Lyt‐2 plus complement, too, were incapable of inducing a negative AE; instead, addition of anti‐Lyt‐2‐treated T cells to B cells that differed either at all of H‐2, at K plus I‐A, or at I‐a alone consistently led to the induction of a strong positive AE. Only a syngeneic‐like response was induced, however, when anti‐Lyt‐2 and complement‐treated T cells were ad