The effects of serotonin (5-HT) on intracellular calcium activity ([Ca2+]i) in epithelial cells from rat choroid plexuses were examined. Experiments were performed on isolated cells which had been maintained in primary culture. ([Ca2+]i) was measured using micro-spectrofluorimetric techniques and the fluorescent indicator Fura-2. 5-HT was found to increase [Ca2+]i in a dose dependent manner. The [Ca2+]i response was biphasic, with an initial peak of [Ca2+]i (due to release from intracellular stores), followed by an elevated plateau phase (the result of calcium influx). The effect of 1 microM 5-HT was inhibited by mesulergine and mianserin (50 nM), which are antagonists of the 5-HT2C receptor. Spiperone and ketanserin (200 nM), less specific 5-HT2 receptor blockers, caused only a slight reduction in the response to 1 microM 5-HT. The [Ca2+]i response decreased upon repeated challenges with 1 microM 5-HT, probably as a result of receptor desensitisation. Taken together, the data suggest that 5-HT acts at 5-HT2C receptors to increase [Ca2+]i in choroid plexus epithelial cells, both by liberating Ca2+ from intracellular stores and by activating a Ca2+ influx pathway.