Effects of the antiepileptic drug valproate on sodium and potassium currents in the nodal membrane of peripheral nerve fibers of Xenopus laevis were determined by voltage- and current-clamp experiments. Under voltage-clamp conditions, a reduction of both sodium and potassium conductance (in a ratio of 2:1) was observed. Typically, 2.4 mM (400 mg/L) valproate reduced the sodium current 54% and the potassium current 26%, at a membrane potential of 5 mV. Valproate did not affect the leakage conductance. The reduction of potassium conductance was voltage dependent, being more pronounced at more positive membrane potentials. For the sodium system, a voltage dependency of the blockage could not be established. Under current-clamp conditions, valproate caused a reduction of excitability of nerve membrane: amplitude of the action potential and maximum rate of rise were decreased, whereas threshold potential was increased. The ability to follow high-frequency stimulation was impaired.