The effects of serotonin (5-HT) on intracellular calcium activity ([Ca 2 + ] i ) in epithelial cells from rat choroid plexuses were examined. Experiments were performed on isolated cells which had been maintained in primary culture. [Ca 2 + ] i was measured using micro-spectrofluorimetric techniques and the fluorescent indicator Fura-2. 5-HT was found to increase [Ca 2 + ] i in a dose dependent manner. The [Ca 2 + ] i response was biphasic, with an initial peak of [Ca 2 + ] i (due to release from intracellular stores), followed by an elevated plateau phase (the result of calcium influx). The effect of 1 μM 5-HT was inhibited by mesulergine and mianserin (50 nM), which are antagonists of the 5-HT 2 c receptor. Spiperone and ketanserin (200 nM), less specific 5-HT 2 receptor blockers, caused only a slight reduction in the response to 1 μM 5-HT. The [Ca 2 + ] i response decreased upon repeated challenges with 1 μM 5-HT, probably as a result of receptor desensitisation. Taken together, the data suggest that 5-HT acts at 5-HT 2 c receptors to increase [Ca 2 + ] i in choroid plexus epithelial cells, both by liberating Ca 2 + from intracellular stores and by activating a Ca 2 + influx pathway.