A high-active I antigen was isolated from human red cells after papainization. Investigations on its chemical composition and its serological properties are reported. 1. The I antigen activity was clearly demonstrated by hemagglutination inhibition studies and by the immuno-double-diffusion with all available anti-I sera. 2. The I antigen did not react with other antibodies directed against red cell antigens thus proving its specificity. Any relationships to antigen activities within the Pr-1/Pr-2, MN, and ABO systems could be excluded. 3. The substance was shown to be a glycoprotein and not a glycolipid. This was confirmed by different delipidation procedures promoting always an increase of I activity. The delipidized material contained only traces of fatty acids, and did not move on thin-layer chromatography in solvent systems normally used for glycolipid development. 4. The I determinant resides on alkali-stable oligosaccharide chains. The main sugars are galactose and N-acetylglucosamine which might be involved in the immunodeterminants.