The screening of ligands for membrane receptor proteins is central to the discovery of new pharmaceutical drugs. We present a general method to reversibly attach receptor proteins via an affinity tag to a quartz surface and subsequently detect with high sensitivity the real-time binding of ligands by total internal reflection fluorescence. A serotonin-gated ion channel protein was immobilized, and the binding of a fluorescent ligand was investigated. The affinity and the kinetic parameters of binding were measured, and the effect of unlabeled compds. was detd. by competition. The pharmacol. of the immobilized receptor was identical to that of the native receptor. The affinity of unlabeled ligands was rapidly and effectively detd. The method described here is generally applicable for membrane proteins and opens new ways for the discovery of pharmacol. active compds. [on SciFinder (R)]