The frequency of spontaneous action potentials (SAP) is important in the regulation of hormone secretion. The decrease in K<sup>+</sup> conductance is known as a primary mechanism for increasing SAP frequency. To investigate the nature of K<sup>+</sup> channels that contribute to the frequency regulation of the SAP in rat clonal pituitary GH<sub>3</sub> cells, the effect of various K<sup>+</sup> channel blockers on the SAP and membrane currents were recorded using the patch-clamp technique. A classical inward rectifying K<sup>+</sup> channel blocker, Cs<sup>+</sup> (5 m M), caused an increase in firing frequency and depolarization in after-hyperpolarization (AHP) voltage. An ether-a-go-go (erg) type K<sup>+</sup> channel blocker, E-4031 (5 µ M), caused no significant effect on the SAP. Tetraethylammonium (TEA, 10 m M) decreased firing frequency and increased the duration of SAP. These effects were not changed by the presence of high concentration of Ca<sup>2+</sup> buffer (10 m M EGTA or BAPTA) in pipette solutions. In voltage-clamp experiments, Cs<sup>+</sup> and E-4031 did not affect outwardly rectifying K<sup>+</sup> currents, but significantly inhibited inwardly rectifying K<sup>+</sup> currents recorded in isotonic K<sup>+</sup> solution. However, the kinetics of Cs<sup>+</sup>-sensitive current and E-4031-sensitive current were distinctive: the time to peak was more immediate and the decay rate was slower in Cs<sup>+</sup>-sensitive current than in E-4031-sensitive current. These results imply that Cs<sup>+</sup> and E-4031 inhibit the distinct components of inwardly rectifying K<sup>+</sup> currents, and that the contribution of the Cs<sup>+</sup>-sensitive current can be immediate on repolarization and can last more effectively over pacemaking potential range than E-4031-sensitive current.