Receptors alternate between resting↔ active conformations that bind agonists with low↔ high affinity. Here, we define a new agonist attribute, energy efficiency (η), as the fraction of ligand-binding energy converted into the mechanical work of the activation conformational change. η depends only on the resting/active agonist-binding energy ratio. In a plot of activation energy versus binding energy (an “efficiency” plot), the slope gives η and the y intercept gives the receptor’s intrinsic activation energy (without agonists; ΔG 0). We used single-channel electrophysiology to estimate η for eight different agonists and ΔG 0 in human endplate acetylcholine receptors (AChRs). From published equilibrium constants, we also estimated η for agonists of K Ca 1.1 (BK channels) and muscarinic, γ-aminobutyric acid, glutamate, glycine, and aryl-hydrocarbon receptors, and ΔG 0 for all of these except K Ca 1.1. Regarding AChRs, η is 48–56% for agonists related structurally to acetylcholine but is only∼ 39% for agonists related to epibatidine; ΔG 0 is 8.4 kcal/mol in adult and 9.6 kcal/mol in fetal receptors. Efficiency plots for all of the above receptors are approximately linear, with η values between 12% and 57% and ΔG 0 values between 2 and 12 kcal/mol. Efficiency appears to be a general attribute of agonist action at receptor binding sites that is useful for understanding binding mechanisms, categorizing agonists, and estimating concentration–response relationships.