The 1973 discovery of lingual lipase, which is secreted by lingual serous glands and hydrolyzes medium- and long-chain triglycerides in the stomach, has renewed interest in the gastric phase of fat digestion. In humans, lipase is present in the serous (von Ebner) glands of the tongue, where it is localized in zymogen granules. In the stomach, the highest lipase activity is in the body. By immunocytochemistry, gastric lipase is confined to the chief cells of the fundic mucosa and is colocalized with pepsin. Human lipase purified from lingual serous glands or gastric juice has a MW of 45k to 51K but tends to aggregate (MW 270-300K and 500K) and is highly hydrophobic. Secretion of gastric lipase appears to be stimulated by at least two receptor mechanisms. It has been suggested that the products of gastric lipolysis maintain the sterility of the gastrointestinal tract. These enzymes are essential for the digestion of milk fat in the newborn because, contrary to other digestive lipases (pancreatic or milk digestive lipase), lingual and gastric lipases can penetrate into the milk fat globule and initiate the digestive process. Lingual and gastric lipase activity has been found in subjects with cystic fibrosis and appears to continue in the upper small intestine in these patients, perhaps replacing some of the missing pancreatic lipase. It is possible that lingual and gastric lipase supplements would be more effective in preventing steatorrhea in these patients than are the pancreatic enzyme supplements now given. The same therapeutic utility might be obtained in patients with alcoholic pancreatic insufficiency.