In previous work we showed that programed cell death (PCD) in thymocytes is mediated by a sustained increase in cytosolic Ca2+ concentration, resulting in the activation of an endogenous endonuclease, DNA fragmentation, and cell death. In this study we investigated the roles of Ca2+ and DNA fragmentation in target cell killing by natural killer (NK) cells. The effector cells induced a rapid, sustained increase in cytosolic Ca2+ concentration in Jurkat target cells. Buffering the target cell cytosolic Ca2+ with the Ca2+‐selective dye, quin‐2, prevented target cell killing. Extensive DNA fragmentation was associated with killing in every target tested, and this response was also blocked by quin‐2. The endonuclease inhibitor, aurintricarboxylic acid, inhibited both DNA fragmentation and killing without influencing the Ca2+ increase in target cells. Thus, it is concluded that NK cell killing depends on a Ca2+ increase and appears to involve endogenous endonuclease activation in target cells.— McConkev. D. J.; Chow, S. C.; Orrenius, S.; Jondal, M. NK cell‐induced cytotoxicity is dependent on a Ca2+ increase in the target. FASEB J. 4: 2661‐2664; 1990.

McConkey, D. J., Chow, S. C., Orrenius, S., & Jondal, M. (1990). NK cell‐induced cytotoxicity is dependent on a Ca2+ increase in the target. The FASEB Journal, 4(9), 2661–2664. Portico.