The experiments presented herein demonstrate that F1-parent T-B cell cooperation in vivo is significantly diminished by the addition of lymphoid cells of opposite parental type. This inhibition phenomenon is not a straightforward allosuppression mechanism as (a) it can be induced by parental lymphoid cells depleted by T cells, (b) it does not operate on cooperative interactions between homologous T and B cells of opposite parental type, and (c) absolutely requires the presence of F1 cells as participants in the reactions generated. The possible involvement of alloantibodies produced aberrantly under the experimental conditions employed has been ruled out by direct macrophage/antigen-presenting cell components of the reactions has been excluded. Because the presence of parental lymphoid cells only affects cooperative interactions between F1 T cells and B lymphocytes of opposite parental type but has no inhibitory effect on cooperative interactions between homologous F1, T and B cells, this (and other points discussed herein) strongly argues for the existence of one or more subsets of F1 interacting partner cells that are uniquely specific for F1, as distinct from either parental type cell interaction determinants. For reasons discussed, it appears that the most likely mechanism underlying such parental cell-induced inhibitory effects on F1-parent partner cell interactions is the development of anti-self cell interaction structure responses by F1 cells against the relevant self-specific cell-interaction structures of the parental partner cells involved.