Nicotine dose-dependently induced cytotoxicity in human glioma (KG-1-C) and glioblastoma (GBS-1, T98G) cell lines, but could not induce internucleosomal DNA cleavage, in contrast to apoptosing human myelogenous leukemic cell lines. Human glioma/glioblastoma cell lines thus might have a chromatin structure resistant to endonuclease digestion. Nicotine induced a rapid increase in the intracellular calcium concentration. Confocal experiments with Fluo-3 fluorescence revealed that nicotine elevated the free Ca2+ concentration in both nuclear and cytoplasmic regions of the cells, and the elevation of Ca2+ in the nuclear region was more pronounced than that of the cytoplasmic region. The present study suggests that nuclear accumulation of Ca2+ is an important initial step for cell death induction by nicotine.