Studies on gastrointestinal lipolysis have underestimated several important points. In view of recent in vitro data obtained in our laboratories, this review focuses on the role of gastric lipolysis during fat digestion. Polyclonal antibodies generated from purified rat lingual lipase were used to screen a cDNA library prepared from mRNA isolated from the serous glands of rat tongue cloned in E. coli expression vectors. A cDNA clone was isolated and the nucleotide and predicted amino acid sequences obtained. Comparison with the N-terminal amino acid sequence of the purified enzyme confirmed the identity of the cDNA. The amino acid sequence of rat lingual lipase consisted of 377 residues and showed little homology with porcine pancreatic lipase, apart from a short region containing a serine residue at an analogous position to the Ser 152 of the porcine enzyme. Human gastric lipase activity on tributyrin emulsion was detected only in the presence of amphiphiles. This behaviour was in sharp contrast with the strong inhibitory effect of amphiphiles observed on pure pancreatic lipase. To reveal human gastric lipase activity, amphiphiles must be added to human gastric lipase in order to prevent irreversible interfacial denaturation. Human gastric lipase activity was found to be restricted to triacylglycerol/water surface tensions ranging from 8 to 13 dynes/cm. All amphiphiles which decrease interfacial tension to less than 8 dynes/cm act as irreversible inhibitors of human gastric lipase in the absence or presence of bile salts. Our results confirm that human gastric lipase is capable of hydrolysing triacylglycerol in the presence of the bile salts concentration prevailing in the upper small intestine and in the presence of alimentary proteins. These observations could explain the high dietary lipid absorption observed under pancreatic lipase deficiency.