Comparisons were made between the seromucoid (perchloric acid soluble, phosphotungstic acid precipitable glycoprotein) fraction of serum from normal subjects and from patients with malignant neoplastic diseases. The seromucoid of normal human serum was separated into eight (I through VIII) fractions by DEAE-cellulose chromatography using a phosphate buffer gradient. The protein, hexose and hexosamine contents and hexosamine/protein ratios were different for the various fractions. Immunoelectrophoretic activity against commercially available antisera was detected in fractions III to VII of normal seromucoid. The fractions differed from each other in disc electrophoresis patterns. Seromucoid from patients with certain diseases revealed alterations in the above parameters. It is possible that some of the evidence of heterogeneity of the fractions is due to preparative artefacts; however, it is also evident that the seromucoid fractions from pathologic sera differ from normal, despite the same preparative treatments. Malignant neoplasms are characterized by alterations in the fractions eluted early in the scheme and other diseases by fractions eluted in the intermediate range. Immunoelectrophoretic and disc electrophoretic studies further demonstrate qualitative differences between the seromucoid fractions from normal and pathologic states.