The effects of bivalent lead on ion channels activated by kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) were studied using Xenopus oocytes microinjected with mRNA from rat brain. Lead reduced kainate-induced membrane currents in a reversible and dose-dependent manner, without affecting membrane currents induced by AMPA. Lead decreased the kainate currents with a concentration of 0.1 micromol/1 to 0.93 +/- 0.01 and with a concentration of 100 micromol/1 to 0.41 +/- 0.04 of the control values. The blocking effect of lead on kainate responses was voltage dependent. The inhibition was strongest at -90 mV to -70 mV and became weaker at more positive membrane potentials. The effect of lead on the kainate-induced membrane currents remained unchanged when the concentration of kainate was increased. Hence lead probably represents a noncompetitive channel-blocking agent for non-N-methyl-D-aspartate (NMDA) receptor channels activated by kainate.