Cholecystokinin (CCK) is an important hormonal regulator of the digestive process. CCK cells are concentrated in the proximal small intestine, and hormone is secreted into the blood upon the ingestion of food. The physiological actions of CCK include stimulation of pancreatic secretion and gallbladder contraction, regulation of gastric emptying, and induction of satiety. Therefore, in a highly coordinated manner, CCK regulates the ingestion, digestion, and absorption of nutrients. CCK is produced by two separate cell types: endocrine cells of the small intestine and various neurons in the gastrointestinal tract and central nervous system. Accordingly, CCK can function as either a hormone or a neuropeptide. This review focuses on the physiology of the CCK cell in the intestine and, in particular, on how the CCK cell is regulated to secrete its hormone product. The effects of ingested nutrients on the CCK cell and the intracellular messenger systems involved in controlling secretion are reviewed. A summary is provided of recent studies examining the electrophysiological properties of CCK cells and newly discovered proteins that act as releasing factors for CCK, which mediate feedback pathways critical for regulated secretion in the intact organism.