The dodecasaccharide obtained by treating dermatan sulfate with testicular hyaluronidase, chondroitinase AC, and β-glucuronidase was incubated with diluted, normal human serum at pH 4.5 or 7.0 followed by chondro-4-sulfatase at pH 7.0. Analyses of the reaction products indicate release of hexosamine but not further degradation of the substrate. It is concluded that normal human serum possesses an exo-β-N-acetylhexosaminidase active on dermatan sulfate.