The recently defined DEG/ENaC superfamily of sodium channels includes subunits of the amiloride-sensitive epithelial sodium channel (ENaC) of vertebrate colon, lung, kidney, and tongue, a molluscan FMRFamide-gated channel (FaNaC), and the nematode degenerins, which are suspected mechanosensory channels. We have identified two new members of this superfamily (BNaC1 and BNaC2) in a human brain cDNA library. Phylogenetic analysis indicates they are equally divergent from all other members of the DEG/ENaC superfamily and form a new branch or family. Human BNaC1 maps to 17q11.2-12 and hBNaC2 maps to 12q12. Northern blot and mouse brain in situ hybridizations indicate that both genes are coexpressed in most if not all brain neurons, although their patterns of expression vary slightly, and are expressed early in embryogenesis and throughout life. By analogy to the ENaCs and the degenerins, which form heteromultimeric channels, BNaC1 and BNaC2 may be subunits of the same channel.