1. The effect of 4-aminopyridine (4-AP) on the K outward and inward currents in perfused giant axons of Loligo forbesi has been studied with the voltage-clamp technique.2. Small internal or external 4-AP concentrations (10-100 muM) considerably delay the rise of the K outward current. Repetitive pulsing with a pulse interval of 0.1-5 sec leads to a faster rise of the K current; in 10 muM 4-AP a small effect is visible even with a pulse interval of 60 sec.3. The phenomenon has been studied quantitatively by using a prepulse of varying height and duration, followed after 5 sec by a constant test pulse. The effect of changing the holding potential has been investigated.4. The effect of repetitive pulsing disappears in higher 4-AP concentrations; 1-10 mM 4-AP markedly reduce the size of the K outward current; the blocking effect is less pronounced for large depolarizing pulses than for small.5. In K-rich sea water 4-AP reduces both the K outward current and the K inward current; the blocking effect on the K outward current is smaller than in K-free sea water.6. The K outward current in fibres treated with 10 muM 4-AP and immersed in K-rich sea water is increased and accelerated by repetitive depolarizing pulses. The effect of repetitive pulsing is not dependent on the size of the K outward current (which can be increased by removing K inactivation).7. The effect of repetitive pulsing and the voltage dependence of the 4-AP block can be explained by the hypothesis that 4-AP molecules are displaced from their blocking sites during the pulse and slowly rebound afterwards. Removal of the 4-AP block by a depolarizing pulse seems to be a direct effect of the potential during the pulse and not related to K current.