Publisher Summary This chapter presents a progress report on the acetylcholine receptor (ACHR). All approaches to the ACHR begin with the response of cells to ACH and the modification of this response. The binding properties of the ACHR are inferred from the variation of the response as a function of the concentration of ACH and of its congeners. The occupation of binding sites is usually taken to be determined by the Langmuir adsorption isotherm, formally equivalent to the Michaelis–Menten equation. The response to agonists is assumed to increase with increasing occupation. If the response was linearly proportional to occupation, then the equilibrium dissociation constant for an activator–ACHR complex would be equal to the concentration of activator eliciting a half-maximal response. One approach to the structure of the binding site is to model it to accommodate potent activators and competitive inhibitors. Those aspects of the structure of these ligands that confer potency are determined and the corresponding structure is inferred for the site. Hydrophilic substitutents, as in choline or in p-carboxyphenyltrimethylammonium, apparently strongly inhibit binding, and such compounds are neither activators nor inhibitors. From these results, it appears that there is a subsite of hydrophobic interaction about 1 nm from the negative subsite.