We have investigated the role of intestinal fat digestion in fat-induced suppression of gastric acid secretion and gastrin release in the rat. Intraduodenal administration of oleic acid (10%, pH 6.5) and triglyceride (10%, pH 6.5) at a rate of 2 ml/hr resulted in significant suppression of gastric acid secretion and gastrin release stimulated by intragastric perfusion of peptone (0.5%). Diversion of pancreatic juice from the duodenum completely abolished triglyceride-induced inhibition of peptone-stimulated gastric acid secretion and plasma gastrin release, but oleic acid-suppressed gastric acid secretion and gastrin release were unaffected by pancreatic juice diversion. Intraduodenal administration of digested triglyceride, prepared by preincubation with lipase, caused significant suppression of the peptone-induced gastric acid secretion and rise in plasma gastrin levels, even though pancreatic juice was excluded. The results of this study indicate that digestive products of triglyceride by pancreatic juice, especially by lipase, are responsible for the intestinal fat-induced inhibition of gastric acid secretion and gastrin release and that intestinal fat digestion plays a significant role in the mechanism.