Human cytotoxic T lymphocyte (CTL) granules contain an electron-dense core and small membrane vesicles. By immuno-electron microscopy, molecules relevant to CTL-target cell (TC) interactions have been identified on the membranes of the dense core and small vesicles within the granule. Moreover, perforin, the component implicated in the lethal hit, and serine esterases are localized within these granule substructures. In this article Peter Peters and colleagues argue that these observations necessitate a revision of the current model for lethal hit delivery. They suggest that the cytotoxic mediators exocytosed into the cleft between CTL and TC are not in soluble form, but rather are membrane-enveloped. The presence of the CD3-T-cell receptor (TCR) complex, CD8 and possibly other relevant molecules on these membranes may ensure unidirectional delivery of the lethal compounds to the TC.