A method is described for the trace iodination of immunoglobulins and other serum proteins using lactoperoxidase, hydrogen peroxide, and iodide. This enzymic method allows for the incorporation of radioactive iodine into proteins without causing denaturation, as demonstrated by electrophoresis and density-gradient ultracentrifugation. The iodide was found to be bound to tyrosyl residues, as shown by tryptic hydrolysis and peptide mapping. Proteins vary in their susceptibility to iodination, with human γG immunoglobulin being more readily iodinated than α2-macroglobulin. Lactoperoxidase catalyzes iodination more efficiently than horseradish peroxidase. The method provides a gentle and effective way to label proteins with high specific radioactivity, which is useful for biochemical and immunological studies. The method was applied to various proteins, including immunoglobulins, albumin, and bacterial flagellins, with no evidence of denaturation. The results indicate that lactoperoxidase is more effective than horseradish peroxidase in catalyzing iodination. The study highlights the potential of this method for the radioiodination of proteins, particularly immunoglobulins, with high specific radioactivity. The method is suitable for use in biological and biochemical research due to its efficiency and minimal risk of protein denaturation. The study also discusses the possible role of animal peroxidases in the defense mechanism against microbial infection. The method is a valuable tool for the study of protein iodination and has potential applications in medical research.A method is described for the trace iodination of immunoglobulins and other serum proteins using lactoperoxidase, hydrogen peroxide, and iodide. This enzymic method allows for the incorporation of radioactive iodine into proteins without causing denaturation, as demonstrated by electrophoresis and density-gradient ultracentrifugation. The iodide was found to be bound to tyrosyl residues, as shown by tryptic hydrolysis and peptide mapping. Proteins vary in their susceptibility to iodination, with human γG immunoglobulin being more readily iodinated than α2-macroglobulin. Lactoperoxidase catalyzes iodination more efficiently than horseradish peroxidase. The method provides a gentle and effective way to label proteins with high specific radioactivity, which is useful for biochemical and immunological studies. The method was applied to various proteins, including immunoglobulins, albumin, and bacterial flagellins, with no evidence of denaturation. The results indicate that lactoperoxidase is more effective than horseradish peroxidase in catalyzing iodination. The study highlights the potential of this method for the radioiodination of proteins, particularly immunoglobulins, with high specific radioactivity. The method is suitable for use in biological and biochemical research due to its efficiency and minimal risk of protein denaturation. The study also discusses the possible role of animal peroxidases in the defense mechanism against microbial infection. The method is a valuable tool for the study of protein iodination and has potential applications in medical research.