To clarify the functional role of amino acid residues in copper binding and in the maintenance of ceruloplasmin catalytic activity, the protein was chemically modified by iodination. It is shown that addition of 20 mol iodine per 1 mol ceruloplasmin mainly produces iodination of tyrosine residues, while the protein modification by higher iodine concentrations (60 mol and more per 1 mol protein) leads also to iodination of histidine. Iodination of ceruloplasmin is followed by loss of copper and the oxidase activity. There is a correlation between copper loss and ceruloplasmin catalytic activity and iodinated histidine content at high concentrations of iodine in the medium. It appears that tyrosine residues are involved in maintaining the active conformational state of ceruloplasmin, while histidine residues directly bind copper in its catalytic center. Peptide maps for 131I‐labeled ceruloplasmin show that most tyrosine peptides of the protein iodinated at small iodine concentrations are localized in the region of acid and alkaline peptides. Histidine peptides, whose iodination in accompanied by decrease in the oxidase activity and copper content, are mainly localized in the neutral peptide region. One of the neutral peptides having a well‐defined Pauly reaction was isolated in a pure form. N‐ and C‐terminal amino acids of the peptide and its amino acid composition were determined.