Induction of an allogeneic cytotoxic T lymphocyte (CTL) response is dependent, in part, on uptake and processing of the class I alloantigen by antigen‐presenting cells and subsequent Ia‐restricted recognition of the alloantigen by helper T cells, resulting in lymphokine production. The nature of the antigen‐processing event has been investigated using reconstituted membranes to replace the antigen‐presenting cells in the generation of a secondary allogeneic CTL response. Membranes were isolated from an Iad‐positive antigen presenting B cell lymphoma (D2N), detergent solubilized and then reconstituted together with affinity‐purified H‐2Kk antigen in the presence of protease inhibitors. These reconstituted vesicles, containing both syngeneic Ia and alloantigen, were able to induce the helper T cell arm of the CTL response in cultures depleted of antigen‐presenting cells. A variety of control experiments provided strong evidence that the helper T cells recognized the H‐2Kk, probably in its native form, in an Ia‐restricted manner on the vesicles, while the pre‐CTL can directly recognize H‐2Kk. Recognition was only effective if both the Ia and alloantigen were inserted into the same membrane bilayer. The results strongly suggest that the obligatory antigen processing event required for helper T cell recognition of alloantigen is simply the insertion of the alloantigen into the same membrane bilayer as the syngeneic Ia restricting element.