The primary structures of the Electrophorus electroplax sodium channel and two distinct sodium channel large polypeptides from rat brain have been deduced by cloning and sequencing the cDNAs. The sodium channel molecule contains four internal repeats with homologous amino acid sequences, which are oriented presumably in a pseudosymmetric fashion across the membrane, thus forming the channel. The mRNAs generated by transcription of the cloned cDNAs encoding the rat brain sodium channel large polypeptides, when injected into Xenopus oocytes, direct the formation of functional sodium channels. The transmembrane topology of the sodium channel molecule and the structure that may be involved in the voltage-dependent gating of the channel are discussed.