The properties of triphenyltin (TPT) in increasing intracellular Ca2+([Ca2+]i) of thymocytes was studied, in comparison with those of A23187, by the use of fluorescent dyes to monitor membrane potential and [Ca2+]i. Both 1 muM TPT and 30 nM A23187 increased the [Ca2+]i associated with the hyperpolarization mediated by Ca2+-dependent K+ conductance. The time course for the TPT-induced increase in the [Ca2+]i was much slower than that of A23187. When the external Ca2+ ([Ca2+]o) was removed, TPT produced a slight, but persistent, increase in the [Ca+]i while A23187 caused only a transient increase in the [Ca2+]i. Reintroduction of Ca2+ to the external solution produced an increase in [Ca2+]i in both cases. Therefore, these results suggested that the increase in the [Ca2+]i of thymocytes induced by TPT and A23187 was dependent on the presence of [Ca2+]o and an intracellular Ca store. The potency of TPT in increasing the [Ca2+]i was greater than those of diphenyltin and monophenyltin, suggesting an involvement of the lipophilic property of organotins in increasing [Ca2+]i. The TPT-induced increase in the [Ca2+]i may be partly responsible for the toxicity of TPT on organs and/or organ systems.