An ultrastructural study of the sheep pancreas indicated that secretin, in low dose, stimulated ion and water transport through acinar cells, the evidence including dilatation and vesiculation of rough endoplasmic reticulum, vacuoles, and pale flocculent acinar lumina; that cholecystokinin, in low dose, stimulated incomplete discharge of zymogen from granules producing distorted granule profiles and electron-dense lumina; and that carbachol, in high dose, produced uptake of fluid by acinar cells, evidenced by dilatation of rough endoplasmic reticulum and pale flocculent vacuoles, and discharge of fluid and zymogen by the vacuoles. The ultrastructural findings were consistent with the physiological studies of stimulated pancreatic juice. Secretin induced predominantly fluid secretion, cholecystokinin stimulated viscous juice with a high zymogen concentration, and carbachol produced elevated amylase concentrations with high flow rates. In normal physiological pancreatic secretion, a combined fluid and zymogen secretion by acinar cells would keep the pancreatic juice flowing freely down the acinar tubules. Pancreatic obstruction in cystic fibrosis or chronic alcoholic pancreatitis may arise from excessive degranulation or insufficient water and electrolyte secretion by acinar cells.