Calcium is one of the most important messengers in cells and changes in intracellular calcium homeostasis are involved in pathways, triggering physiologic processes as well as pathological cell functions (apoptotic cell death). It has been shown that cisplatin is capable of triggering apoptosis by activating extrinsic and intrinsic apoptotic pathways. Since these effects are especially dominant in tumor cells, cisplatin is medically used in diverse treatments against colon and lung cancer. However, it remains unclear through which particular mechanisms the drug acts in specific forms of maligne cells. In this study we compare intracellular calcium changes induced by cisplatin in U2-OS and HeLa-S3 cells using calcium-sensitive dye fluo-4/AM and laser scanning microscopy (LSM). Clinical relevant concentrations were applied. Low concentrations (threshold 0.001 mM) of cisplatin increased concentration dependently [Ca²⁺]_i in HeLa-S3 cells but not in U2-OS cells, while carboplatin had no effect. The increase of [Ca²⁺]_i depends on extracellular calcium. Preincubation with the IP₃-receptor antagonist 2-APB (50 mM) abolished the cisplatin induced increase of the intracellular calcium concentration, indicating a signalling pathway between this receptor and calcium entry. The use of cisplatin as an anti-cancer drug in specific tumour cell lines could be attributed at least partially to the modulations of [Ca²⁺]_i homeostasis.