Human intestinal maltase and sucrase contain 30 to 40% carbohydrate by weight and are resistant to proteolytic digestion by papain. The major carbohydrates associated with these enzymes are fucose, galactose, and hexosamines. The purified disaccharidases demonstrate blood group antigenicity of great potency, as little as 8 x 10-9 to 1.5 x 10-7 M inhibiting red cell agglutination. The blood group reactivity is not the result of contamination by blood group substance because: type specific antibody causes a shift of enzyme activity on sucrose gradients; antibody changes the R(f) of the enzyme band on acrylamide electrophoresis; and enzyme activity is selectively retained by type specific antibody bound to Sepharose. Rat intestinal disaccharidases contain 15 to 20% carbohydrate and do not have blood group reactivity, yet are papain resistant. Alkali treatment in the presence of sodium borohydride produces heterogeneous protein fragments without carbohydrate (18,000 to 25,000 mol wt) and a carbohydrate fragment with a molecular weight of about 1,800. It is concluded that human intestinal disaccharidases are glycoproteins and that blood group reactivity is contained in the oligosaccharide side chain covalently linked to the enzyme. This is the first demonstration of blood group antigenicity associated with a functioning protein molecule. The disaccharidases may account for some of the insoluble blood group reactivity found in intestinal tissue.