LIGAND-gated ion channels, a major class of cell-surface proteins, have a pseudosymmetric structure with five highly homologous subunits arranged around a central ion pore¹. The correct assembly of each channel, whose subunit composition varies with cell type and stage of development, requires specific recognition between the subunits^2–4. Assembly of the pentameric form of the acetylcholine receptor from adult muscle (AChR; α₂βɛδ) proceeds by a stepwise pathway starting with the formation of the hetero-dimers, αe and α δ. The heterodimers then associate with the β subunit and with each other to form the complete receptor^5–7,21. We have now determined which parts of the subunits mediate the interactions during assembly of the adult form of the receptor from mouse muscle by using a chimaeric subunit in which the N-terminal and C-terminal extracellular domains are derived from the ɛ subunit with the remainder from the β subunit. The e and β subunits were chosen because the subunit forms a heterodimer with the a subunit in the pathway for assembly of the receptor,whereas the β subunit does not. The ɛ_β chimaera can substitute for the ɛ but not the β subunit in the oligomeric receptor, indicating that the a subunit specifically recognizes an extracellular domain of the e subunit.