Lidocaine effects were studied at the single channel level on batrachotoxin-activated eel electroplax (muscle-derived) and on rat brain sodium channels in planar lipid bilayers to investigate whether these effects were the same on structurally different sodium channels. Lidocaine blocked the open state of brain channels with the same voltage dependence, but with 15-times as high a potency as muscle-derived channels. In brain channels, but not muscle-derived ones, the level of the open channel block showed periods of relief. Lidocaine at microM concentrations stabilized the highest conductance state in both channel types and at mM concentrations stabilized subconductance-like states in electroplax, but not in brain channels. In both channel types, lidocaine increased the lifetime and rate of entry to a long-nonconducting state. Since both channel types were studied under identical lipid and ionic conditions, the observed functional differences in the lidocaine action (effects, potency) must reflect channel structural differences.