Cytotoxic T lymphocytes (CTLs) which carry the CD8 antigen recognize antigens that are presented on target cells by the class I major histocompatibility complex. CTLs are responsible for the killing of antigen-bearing target cells, such as virus-infected cells. Although CTL effecters can act alone when killing target cells, their differentiation from naive CD8-positive T cells is often dependent on ＇help＇ from CD4-positive helper T (T-H) cells(1-4).Furthermore, for effective CTL priming, this help must be provided in a cognate manner, such that both the T-H cell and the CTL recognize antigen on the same antigen-presenting cell(2,4). One explanation for this requirement is that T-H cells are needed to convert the antigen-presenting cell into a cell that is fully competent to prime CTL5. Here we show that signalling through CD40 on the antigen-presenting cells can replace the requirement for T-H cells, indicating that T-cell ＇help＇, at least for generation of CTLs by cross-priming, is mediated by signalling through CD40 on the antigen-presenting cell.