Natural killer (NK) cells in the human are a population of large granular lymphocytes (LGL) with at least one unique surface antigen not expressed on cells of other lineages. NK-target-cell interaction appears to involve carbohydrate recognition and, following binding, the NK cells are induced to generate O2-, transmethylate membrane phospholipids, and activate phospholipase A2. Some or all of these activities trigger a cascade of events which ultimately leads to the secretion of a substance toxic to the target cell. A variety of genes controls various steps in this cytolytic pathway. There is a good deal of evidence in the mouse, and some in the human, that NK cells play a role in host surveillance against tumor development, resistance to viral infections, and, possibly, hematopoietic regulation.