Adoptive transfer of anti-H-2Db-primed B cells combined with anti-minor histocompatibility antigen-primed T cells enables the effect of linked and unlinked alloantigen to be compared. Over an extensive dose range the unlinked antigen proved ineffective. In a previously described, exactly comparable system for assessing the same effect on cytotoxic T cell precursors, low doses of linked antigen had proved approximately equally effective, but high doses of unlinked antigen had proved effective. This contrast supports the hypothesis that whereas T-B collaboration is mediated by two-cell-type clusters, collaboration between T cells requires formation of three-cell-type clusters.