Arsenic trioxide (As₂O₃) and cisplatin (cPt) are used as anticancer drugs. As we have recently shown, both substances increase the intracellular calcium concentration ([Ca²⁺]_i) in some specific cell lines (Florea et al.; Splettstoesser et al., this volume). As Ca²⁺ is one of the most important intracellular messengers, it induces physiological as well as pathological cell processes (e.g. apoptosis and necrosis) and a modulation of [Ca²⁺]_i homeostasis might also be involved for the beneficial effects of these substances in maligne cells. Interestingly, both substances increase [Ca²⁺]_i by different mechanisms: while As₂O₃ depletes the intracellular calcium stores, cPt induces Ca²⁺ entry from extracellular space. Therefore, we analyze the increase of [Ca²⁺]_i after co-application of cPt and As₂O₃ in human neuroblastoma SY-5Y cells using the calcium sensitive dye fluo-4 and confocal laser scanning microscopy. A single application of cPt (1mM) or As₂O₃ (1mM) increased [Ca ²⁺]_i by 42±15%, or 37±31%, respectively. The additional application of As₂O₃ to cPt or cPt to As₂O₃ at the same concentration (1mM) resulted in a clear further increase of [Ca²⁺]_i (114±25%, or 70±57%, respectively), which could not be reached by increasing the concentration of cPt or As₂O₃ to the double concentration. Therefore we conclude, that due to the different mechanisms by which cPt or As₂O₃ increase [Ca²⁺]_i, their co-application results in an additive increase of [Ca²⁺]_i. This might be important for their use as anti cancer drugs.