The site of adenosine 3′,5′-monophosphate-mediated fluid and electrolyte secretion across mammalian large intestine was found to be the crypts of Lieberkühn by means of two techniques. First, the formation of fluid droplets was visualized on the oil-covered mucosal surface directly over crypt duct openings when secretion was stimulated. Second, microelectrode impalement of individual surface and crypt cells revealed that only the crypt cells produced a pattern of secretagogue-induced alterations in membrane potential and resistance that was characteristic of secretory epithelia.