In this study, we investigated agents that increased intracellular calcium levels and their correlation with apoptotic cell death induction. We used rat astrocytes to investigate the increase in cytosolic Ca2+, (Ca-c(2+)) and apoptosis induction by drugs that mobilize Ca2+ from different sources. We observed that thapsigargin (Thap), caffeine (Caff) and FCCP which caused similar increases in Ca-c(2+) levels (30-40%), also induced similar apoptotic rates (30-35%). On the other hand, antimycin (Anti), staurosporine (STS) and ethanol (Eth) promoted higher increases in Ca-c(2+) (55-65 %) and higher apoptotic rates (55-85%). Eth induced cell death in a concentration- and time-dependent manner. After treatment with Eth plus Caff for 6, 12 and 24 h, these effects were strongly potentiated. Results suggest that there might be a correlation between Ca-c(2+) increase and the rate of apoptosis. It is possible that Eth induces cell death by activation of more than one pathway and Ca-c(2+) might be one of the elements involved. The present work indicates that Ca-c(2+) can potentiate death by ethanol in rat astrocytes. (c) 2005 Elsevier Ireland Ltd. All rights reserved.