According to our working hypothesis, the terminal nerve (TN)-gonadotropin releasing hormone (GnRH) system functions as a neuromodulatory system that regulates many long-lasting changes in animal behaviors. We have already shown by using in vitro whole brain preparations of a small fish (dwarf gourami) that the pacemaker activities of TN-GnRH neurons are modulated biphasically by salmon GnRH, which is the same molecular species of GnRH produced by TN-GnRH neurons themselves; the modulation consists of initial transient decrease and late increase of firing frequency. In the preset study, we investigated the possible involvement of Ca² release from intracellular store and voltage dependent Ca² currents in the modulation of pacemaker activities. Pharmacological blockade of Ca² release from intracellular stores or apamin-sensitive Ca² -activated K current inhibited the initial transient decrease of firing frequency by sGnRH. On the other hand, bath application of Ca² channel blockers Ni² or La³ slowed down the pacemaker frequency and attenuated the rate of the late increase of pacemaker frequency by GnRH. Furthermore, voltage-clamp experiments suggested that low-voltage-activated (LVA) Ca² current and high-voltage-activated (HVA) Ca² current were present in the TN-GnRH neurons, and bath application of GnRH shifted the activation threshold of HVA Ca² current to more negative potentials. These results suggest that (1) sGnRH induces Ca² release from intracellular stores and activates apamin-sensitive Ca² -activated K current so that it decreases the frequency of pacemaker activity in the initial phase, (2) some kinds of Ca² currents contribute to the generation and modulation of pacemaker activities, and (3) HVA Ca² current is facilitated by sGnRH so that it increases the frequency of pacemaker activity in the late phase.