The effects of bepridil, an antianginal agent with antiarrhythmic action, on voltage-dependent K+ currents in the CA1 pyramidal neurons acutely isolated from rat hippocampus were studied by means of whole-cell patch clamp techniques. Current recordings were made in the presence of TTX to block Na+ current. Depolarizing test pulses activated two components of outward K+ currents: a rapidly activating and inactivating component, IA; and a delayed component, IK. Results showed that bepridil reduced the amplitude of IA and IK, and exerted its inhibitory action in time- and dose-dependent manner. Half-blocking concentrations (IC50) of bepridil on IA and IK were 17.8 microM and 1.7 microM, respectively. 10 microM bepridil suppressed IA and IK by 46.7% and 77.1% at +30 mV of depolarization, respectively. When IK was activated nearly uncontaminated with IA by holding at -50 mV, 10 microM bepridil inhibited IK by 71.6% at +30 mV of depolarization; 10 microM bepridil positively shifted the voltage-dependent of activation curves of IA and IK 12.1 mV and 28.7 mV, respectively. These results suggested that blockade on K+ currents by bepridil is preferential for IK, and contributes to the protection brain against ischemic damage.