The receptor occupancy model, which describes agonist and competitive antagonists, was built on the work of Langley, Hill, and Clark. The occupancy model was the first model put forward by Clark to explain the activity of drugs at receptors and quantified the relationship between drug concentration and observed effect. It is based on mass-action kinetics and attempts to link the action of a drug to the proportion of receptors occupied by that drug at equilibrium.  In particular, the magnitude of the response is directly proportional to the amount of drug bound, and the maximum response would be elicited once all receptors were occupied at equilibrium. He applied mathematical approaches used in enzyme kinetics systematically to the effects of chemicals on tissues.
He showed that for many drugs, the relationship between drug concentration and biological effect corresponded to a hyperbolic curve, similar to that representing the adsorption of a gas onto a metal surface and fitted the Hill–Langmuir equation. Clark, together with Gaddum, was the first to introduce the log concentration–effect curve and described the now-familiar parallel shift of the log concentration–effect curve produced by a competitive antagonist. Attempts to separate the binding phenomenon and activation phenomenon were made by Ariëns in 1954 and by Stephenson in 1956 to account for the intrinsic activity (efficacy) of a drug (that is, its ability to induce an effect after binding). Classic occupational models of receptor activation failed to provide evidence to directly support the idea that receptor occupancy follows a Langmuir curve as the model assumed leading to the development of alternative models to explain drug behaviour.