Before 1970, lymphocytes were classified as either of 2 cell types, T cells or B cells. Using the new T-cell antigen, Thy-1, the cytotoxic lymphocyte induced after alloimmunization was identified as a T cell. With the discovery that unimmunized lymphocytes could kill antibody-coated target cells, the search began to identify the effector cell. In 1973, while in Ivan Roitt's laboratory, we discovered "null" killer cells that were neither T nor B cells, indicating that a new class of killer lymphocytes exists. The following year, with John Playfair, we reported an unusual type of "spontaneous" cytotoxicity in which "null" lymphocytes kill target cells without prior immunization and without antibody. In 1975, Rolf Keissling and colleagues in Sweden described a similar natural cytotoxicity and determined that the killer cell was genetically regulated, and killed many types of tumours. Keissling named the effector cell a "natural" killer (NK) cell. In 1976, we proposed that resistance to tumours is T-cell independent and is mediated by a natural immune mechanism requiring NK cells. With the discovery of the NK-deficient "beige" (bg/bg) mouse, the importance of NK cells in control of hematogenous metastasis was confirmed.