There are two competing, but probably really complementary, models for the mechanism of cell-mediated cytotoxicity. One depends upon contact-mediated transmembrane signaling, and the other on the exocytosis of toxic materials by the killer cell. There is exciting news on both fronts. Transmembrane signaling has been shown to involve the surface molecule Fas/APO-1 on targets and its ligand on cytotoxic T cells. The Fas ligand has been cloned, and is a member of the tumor necrosis factor family. The major cytolytic molecule in the exocytosis pathway is perforin; perforin knock-out mice have been produced, and they display many intriguing abnormalities. It has been a bumper year for cytotoxicologists.