The action of lead (Pb2+) on cloned voltage-operated potassium channels of the rat brain was investigated in oocytes of Xenopus laevis. Pb2+ was found to decrease the potassium currents. This effect was due to a shift of the current-voltage relation in a positive direction (up to 30 mV). The Pb2+ effect appeared at a threshold concentration of about 0.1 mumol/l and was maximal at a concentration of about 30 mumol/l. At a potential of -30 mV, the concentration needed for a 50% reduction of the potassium current was 1.0 mumol/l. The depressant effect of Pb2+ was obtained with all potassium channels tested (Kv1.1, Kv1.2, Kv1.4, Kv2.1, Kv3.4). It was minimal for the Kv2.1 channel and maximal for the Kv1.1 channel at potentials negative to 0 mV. An effect comparable with that of Pb2+ could not be induced by the application of magnesium or calcium. The external application of Pb2+ led to a decrease of potassium currents in outside-out but not in inside-out membrane patches. Overall, Pb2+ had a significant effect on the potassium channels which may contribute to the mechanisms of Pb2+ neurotoxicity.