We have looked at several anticonvulsant drugs regarding their potency for basal block of sodium channels in both skeletal muscle and myelinated nerve preparations under voltage clamp conditions. There is an inverse relationship observed between the half-blocking concentration of each drug and its lipid distribution coefficient. Furthermore the anticonvulsants which are cyclic amides show a systematically weaker potency for blocking channels than do local anesthetics (linear amides) of comparable solubility. Additional kinetic characterizations of drug block are described that may contribute to accumulation of frequency-dependent block and to the appearance of 'inactivation shift' phenomena. Finally, evidence is provided showing that phenytoin and carbamazepine (as well as phenobarbital) selectively block the inactive form of closed sodium channels, thus giving these anticonvulsants a capability for selective action in depolarized tissue.