Cytolytic T lymphocytes (CTLs) kill by inducing apoptosis within minutes after contact with their target in a process requiring neither new gene expression nor protein synthesis of the target cells. Killer lymphocytes possess at least two molecularly distinct, fast-acting lytic mechanisms. In the first, the granule exocytosis lytic mechanism, the secreted lytic protein perforin produces poly-perforin pores (i.d. 10-20 nm) in the target cell's membrane. Granzymes, cosecreted with perforin, are thought to penetrate the target cell through these pores to bring about apoptosis by activating the ICE/ced-3 pathway of apoptosis induction. The second, nonsecretory lytic mechanism involves neither the secretion nor the action of the pore-forming protein perforin nor of cosecreted granzymes. Instead, a surface membrane ligand of the killer cell (Fas-ligand), cross-linking with the apoptosis-inducing target cell surface death receptor Fas (CD95), triggers a cascade of intracellular protein-protein interactions and proteolytic activities involving ICE/ced-3 and culminating in apoptosis of the target cell. Despite fundamental differences in the onset of apoptosis induced by perforin/granzyme and by triggering the Fas pathway, the downstream sequences of events that culminate in apoptosis appear to be quite similar. Although the two CTL lytic pathways appear to work in concert, the specific function of each mechanism and its regulation in a given setting in vivo and even in vitro remain to be elucidated.