Perforin has a key role in cell-mediated cytotoxicity. It is a 70 kDa cytolytic protein that is expressed in the cytoplasmic granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. CTLs are involved in eliminating virally infected cells, in anti-tumor immune responses, in allograft rejections, and in some autoimmune diseases. NK cells are important for tumor surveillance and destruction and are involved in allograft rejections. Cytotoxic cells release the contents of their cytotoxic granules, including perforin upon recognition of their target cell. In the presence of calcium, perforin forms transmembrane channels or pores in the membrane of the target cell leading to a cell death that resembles apoptosis. The ability to detect perforin-positive cells with specific antibody should be useful in identifying and understanding perforin-mediated reactions.