Very high concentrations of CA 125 have been found in some ovarian cancer patients after repeated radioimmunodetection with anti-CA 125 antibodies [OC125-F(ab')2]. In one patient we measured a CA 125 concentration of 135,000 kilo-arb. units/L, using an enzyme immunoassay involving OC125 antibodies. With an immunoradiometric assay involving use of two new anti-CA 125 antibodies (B43.13 and B27.1), the CA 125 concentration was 34 kilo-arb. units/L, indicating a discrepancy. The component responsible for the high result in the enzyme immunoassay could be purified by immunoaffinity chromatography on Protein A-Sepharose. Furthermore this component bound to anti-human IgG-Sepharose in the same manner as did the serum IgG fraction. Adsorption of human anti-mouse antibodies present in the serum did not decrease the CA-125-like material. Binding of whole OC125 antibodies to the purified CA-125-like material was inhibited completely in the presence of CA 125 antigen. We infer that the false-positive CA 125 activity is ascribable to a human IgG directed against an idiotope of the OC125 antibody, which was induced by repeated application of OC125 antibodies. To avoid falsely positive results in patients receiving OC125 antibodies, CA 125 should be measured by an assay in which other antibodies are used.