BACKGROUND: The Le(a) and Le(b) antigens are synthesized by cells making exocrine secretions, but it is not well-defined where plasma and red cell Le(a) and Le(b) antigens are made. STUDY DESIGN AND METHODS: This study uses chromatographic and immunochemical methods to extract Le(a) and Le(b) glycolipids from human tissues. RESULTS: Le(a) and Le(b) antigens may be synthesized by both epithelial and mesodermal tissues. Expression of Lewis transferase activity was demonstrated in various tissues, confirming the epistatic interaction by Le and H genes to form the Leb antigen. CONCLUSION: The Le(a) and Le(b) substances found in plasma might originate from the epithelial cells of the digestive tract.