Adults have a high capacity for digestion and absorption of dietary fat. For this sufficient concentration of colipase-dependent pancreatic lipase for digestion, and micellar concentrations of bile salts for product absorption, are required. Relative deficiency of both are therefor considered the major cause of fat malabsorption seen in some newborn, especially preterm, infants. Therefor the observation that fat digestion is initiated in the stomach by pregastric/gastric lipase has gained interest mainly in the neonatal period. To study the properties and physiological function of a pregastric lipase we purified the enzyme from calf pharyngeal tissue. The electrophoretically pure enzyme is a single-chain glycoprotein with Mr ~50,000 D. It crossreacts immunochemically with a lipase of similar size in human gastric juice and, since the two have similar properties also in other respects, we consider the bovine enzyme as useful model for the human counterpart. Since pregastric lipase has an acid pH-optimum and is extensively resistant to proteolysis by pepsin it has properties required for a function in stomach contents. In contrast, it is rapidly inactivated by physiological concentrations of pancreatic proteases and bile salts. Hence, it is not likely that it contributes to fat digestion in duodenal contents. Pregastric lipase has no known cofactor and in contrast to other lipases involved in fat digestion it can by itself hydrolyze human milk triglycerides. This property is thus unique and probably the most essential function for pregastric lipase. On the other hand its activity is susceptible to product inhibition. Thus, in vitro hydrolysis of 2–5% of the substrate (milk) triglyceride is enough to cause complete inhibition. This observation suggests that gastric lipolysis is not mainly of quantitative importance. Interestingly however the low concentration of free fatty acid released by pregastric lipase has an opposite effect on milk triglyceride digestion by colipase-dependent lipase. The latter lipase can by itself not hydrolyze human milk fat globule triglyceride in vitro not even in presence of its cofactor colipase and bile salt. After hydrolysis of a few per cent of milk triglyceride by pregastric lipase the remaining triglyceride is rapidly hydrolyzed by colipase-dependent lipase. This triggering effect of pregastric lipase can be replaced by direct addition of a low concentration of free fatty acid.