Analytical isoelectric focusing in polyacrylamide gel at pH 2.5 to pH 5 was used successfully to detect an acidic protein which can be found in large quantities in the sera of cancer patients but in only small amounts in the sera of healthy persons. The main peak of this acidic protein when obtained from cancer patients revealed a pI of 3.0, while the pI of that obtained from normal subjects was 3.1. The results obtained also demonstrated that qualitative and quantitative differences of such serum acidic proteins discriminate between sera of normal persons and cancer patients. Purification of this acidic protein (pI 3.0) was attempted with cancer ascitic fluids by successive ammonium sulfate precipitation, diethylaminoethyl cellulose column chromatography, Sephadex G-100 gel filtration, and preparative isoelectric focusing. When the purified acidic protein was characterized for physicochemical properties, it was found to have an isoelectric point of 3.0, to have a molecular weight of 50,000, and to contain 31.5% carbohydrate. Its behavior in immunodiffusion and immunoelectrophoresis was indistinguishable from that of normal human alpha 1-acid glycoprotein. However, in gel isoelectric focusing, in molecular weight, and also in carbohydrate content, the acidic protein isolated from cancer ascitic fluid differed from normal alpha 1-acid glycoprotein. Furthermore, this acidic protein was found to suppress both phytohemagglutinin-induced lymphocyte blast formation and mixed-lymphocytes reaction in vitro. The acidic protein, which we called "immunosuppressive acidic protein," and its biological activities were discussed regarding its possible role in the impairment of the immunological surveillance mechanism in the tumor-bearing host.