Beauvericin, a cyclic hexadepsipeptide, is a mycotoxin that can induce cell death in human lymphoblastic leukemia CCRF-CEM cells. Our previous data have shown that beauvericin induces cell death in CCRF-CEM cells in a dose- and time-dependent manner, and that this beauvericin-induced cell death can be prevented by administration of intracellular calcium chelator-BAPTA. Therefore, the intracellular Ca2+ concentration ([Ca2+](i)) may play an important role in beauvericin-induced cell death in CCRF-CEM cells. In this study, the effect of beauvericin on [Ca2+](i) and the possible mechanism responsible for the changes of [Ca2+](i) in CCRF-CEM cells were investigated. Beauvericin caused a rapid and sustained [Ca2+](i) rise in a dose-dependent manner. Excess extracellular Ca2+ facilitated beauvericin-induced [Ca2+](i) rise by adding 1 mM CaCl2 in the bathing medium. On the other hand, beauvericin-induced [Ca2+](i) rise was prevented in Ca2+-free Tyrode's solution by 200 pM EGTA. In addition, beauvericin-induced [Ca2+](i) rise was also attenuated by intracellular Ca2+ chelator-BAPTA/AM. It is worthy to note that neither the voltage-dependent Ca2+ channel blocker, nimodipine, nor depletion of intracellular Ca2+ with thapsigargin, an endoplasmic reticulurn Ca2+ pump inhibitor, has any effect on beauvericin-induced [Ca2+](i) rise. The data from present study indicate that beauvericin acts as a potent Ca2+ Mobilizer by stimulating extracellular Ca2+ influx CCRF-CEM cells. (c) 2005 Elsevier Inc. All rights reserved.