The list of cells with cytotoxic potential now may include small resti
ng T cells, but the exact nature of 'lethal hit delivery' by cytotoxic
T lymphocytes remains elusive. Cell-mediated cytotoxicity by cytotoxi
c T lymphocytes is a complex, multistep process which seems likely to
be mediated by several different pathways. Recent experimental evidenc
e for the functioning of a novel cytotoxic mechanism through a target
cell's surface receptor illustrates and emphasizes the necessity to st
udy the interactions of cytotoxic T lymphocytes and target cells as a
whole. Progress is evident in the description of molecular requirement
s for triggering cytotoxicity, cell-cell contacts and the regulation o
f the effector responses of cytotoxic T lymphocytes by extracellular,
intracellular and granular proteins. Extracellular Ca2+-dependent secr
etion of perforin and protease(s) may explain several aspects of cellu
lar cytotoxicity, whereas the apoptosis-mediating cell surface Fas pro
tein is now implicated in Ca2+-independent cytotoxicity.