Gastrin is one of the principle hormonal mediators of gastric acid secretion, and its cognate receptor (CCK-B) is a member of the superfamily of GPCRs. Patients with hypergastrinemia may present with a variety of symptoms, including gastric ulcers or malignant tumors. Thus, the molecular mechanisms that terminate CCK-B receptor signaling, as well as an ability to measure gastrin bioactivity in a timely manner, have important clinical implications. In order to assess CCK-B receptor regulation, we have constructed a single cell biosensor containing the CCK-B receptor and an arrestin/GFP chimera. The gastrin biosensor responded to both immunologically detectable gastrin-17 and undetectable pentagastrin, and was able to determine the gastrin bioactivity of serum from a patient with clinical hypergastrinemia. We determined that the CCK-B receptor binds arrestin with a pharmacology mirroring CCK-B receptor signaling through inositol phosphate, and that the rate of arrestin dissociation from internalized receptor mirrors receptor recycling to the plasma membrane. Moreover, the CCK-B recycling rate is intermediate between that of Class A GPCRs such as the beta2-adrenergic receptor and Class B GPCRs such as the vasopressin type 2 receptor. Mathematical modeling of these results indicates that a common receptor conformation may underlie both CCK-B signaling and desensitization. In addition to its use in drug screening, this methodology should generalize to other receptors for use in diagnosis and monitoring of bioactive ligands involved in GPCR-based disease.