Quantum dots (QDs) may be useful as novel luminescent markers, but their cytotoxicity has not been fully investigated. In this report, we demonstrate that CdSe-core QDs can induce apoptotic biochemical changes, including JNK activation, loss of mitochondrial membrane potential, mitochondrial release of cytochrome c and activation of caspase-9 and caspase-3 in the IMR-32 human neuroblastoma cell line. Importantly, treatment of IMR-32 cells with CdSe-core QD triggered an increase in reactive oxygen species (ROS) and inhibited survival-related signaling events, such as decreased Ras and Raf-1 protein expression and decreased ERK activation. These apoptotic biochemical changes were not detected in cells treated with ZnS-coated CdSe QDs. Collectively, these results demonstrate that CdSe-core QD treatment of IMR-32 cells induced JNK activation and mitochondrial-dependent apoptotic processes while inhibiting Ras-->ERK survival signaling and that a ZnS coating could effectively reduce QD cytotoxicity.