A number of publications from this and other laboratories have indicated that α-globulinrich fractions isolated from normal mammalian plasma possess immunosuppressive properties both in vivo and in vitro (1–6). The present communication describes a method for the isolation of a fraction from human plasma which is extremely active in the prolongation of skin allograft suvival times in mice and in the prolongation of survival times of xenografts from rats to mice. This fraction which we call N.I.P., normal immunosuppressive protein, migrates in immunoelectrophoresis and in acrylamide gel electrophoresis with the α-globulin bands. The plasma of outdated ACD blood was removed and diluted two and a half times with distilled water. It was then adjusted to pH 5 with glacial acetic acid, and left overnight at 4°C. The fine precipitate which formed was removed by centrifugation. The supernatant was applied to a DEAE-cellulose chromatography column (Whatman, Microgranular, preswollen DE52) previously equilibrated with 0.03 M sodium acetate buffer, pH 5.