Exposure of receptor-rich membrane fragments from Torpedo marmorata to carbamylcholine causes a slow (half-time of 5--10 min) and reversible change of properties of the cholinergic receptor protein manifested by a decrease of the initial rate of Naja nigricollis alpha-[3H]toxin binding in the presence of carbamylcholine. This change corresponds to a 5- to 20-fold increase of affinity for carbamylcholine. Other agonists, acetylcholine, phenyltrimethylammonium, show the same effect but not the antagonists d-tubocurarine and flaxedil. Decamethonium and hexamethonium show little, if any, agonistic effect in vitro on the same membrane fragments but cause the affinity change. This regulatory property can be lost after aging of the preparation of membrane fragments. Since the affinity increase progresses with a similar time course as the decrease of amplitude of the permeability response consecutive to agonist preincubation, it is proposed that, in the membrane at rest, the receptor protein is present under a state of low affinity for agonists and that the reversible stabilization by the agonists of a high affinity state corresponds to the "pharmacological desensitization" of the system as predicted by one of the models of Katz and Thesleff.