BackgroundAn increase in intracellular calcium concentration ([Ca2+]i) in neurons has been proposed as an important effect of volatile anesthetics, because they alter signaling pathways that influence neurotransmission. However, the existing data for anesthetic‐induced increases in [Ca2+]iconflict.MethodsChanges in [Ca2+]iwere measured using fura‐2 fluorescence spectroscopy in rat cortical brain slices at 90, 185, 370, and 705 [micro sign]M isoflurane. To define the causes of an increase in [Ca2+]i, slices were studied in Ca2+‐freemedium, in the presence of Ca2+‐channelblockers, and in the presence of the Ca2+‐releaseinhibitor azumolene. The authors compared the effect of the volatile anesthetic with that of the nonanesthetic compound 1,2‐dichlorohexafluorocyclobutane. Single‐dose experiments in CA1 neurons in hippocampal slices with halothane (360 [micro sign]M) and in acutely dissociated CA1 neurons with halothane (360 [micro sign]M) and isoflurane (445 [micro sign]M) also were performed.ResultsIsoflurane at 0.5, 1, and 2 minimum alveolar concentrations increased basal [Ca2+]iin cortical slices in a dose‐dependent manner (P < 0.05). This increase was not altered by Ca2+‐channelblockers or Ca2+‐freemedium but was reduced 85% by azumolene. The nonanesthetic 1,2‐dichlorohexafluorocyclobutane did not increase [Ca2+] (i). In dissociated CA1 neurons, isoflurane reversibly increased basal [Ca (2+)]iby 15 nM (P < 0.05). Halothane increased [Ca2+]iin dissociated CA1 neurons and CA1 neurons in hippocampal slices by approximately 30 nM (P < 0.05).Conclusions(1) Isoflurane and halothane reversibly increase [Ca2+]iin isolated neurons and in neurons within brain slices. (2) The increase in [Ca2+]iis caused primarily by release from intracellular stores. (3) Increases in [Ca2+]ioccur with anesthetics but not with the nonanesthetic 1,2‐dichlorohexafluorocyclobutane.