Phenytoin, carbamazepine, and lamotrigine are anticonvulsants frequently prescribed in seizure clinics. These drugs all show voltage-dependent inhibition of Na+ currents, which has been implicated as the major mechanism underlying the antiepileptic effect. In this study, I examine the inhibition of Na+ currents by mixtures of different anticonvulsants. Quantitative analysis of the shift of steady state inactivation curve in the presence of multiple drugs argues that one channel can be occupied by only one drug molecule. Moreover, the recovery from inhibition by a mixture of two drugs (a fast-unbinding drug plus a slow-unbinding drug) is faster, or at least not slower, than the recovery from inhibition by the slow-unbinding drug alone. Such kinetic characteristics further strengthen the argument that binding of one anticonvulsant to the Na+ channel precludes binding of the other. It also is found that these anticonvulsants are effective inhibitors of Na+ currents only when applied externally, not internally. Altogether these findings suggest that phenytoin, carbamazepine, and lamotrigine bind to a common receptor located on the extracellular side of the Na+ channel. Because these anticonvulsants all have much higher affinity to the inactivated state than to the resting state of the Na+ channel, the anticonvulsant receptor probably does not exist in the resting state. Thus, there may be correlative conformational changes for the making of the receptor on the extracellular side of the channel during the gating process.