The copper(II)-binding ability of human alpha-fetoproteins, which were purified from umbilical cord serum and from ascites fluid of a hepatoma-bearing patient, was examined by equilibrium dialysis and gel filtration methods. The pH dependence of the copper(II)-binding ability of alpha-fetoprotein was quite similar to that of albumin. Alpha-fetoprotein bound 1 mol of copper(II) ion per mol of protein above pH 6.0 and 0.5 mol of copper(II) ion at pH 5.4, which is close to the pK value of the imidazole group of histidine. Photooxidation of alpha-fetoprotein in the presence of methylene blue resulted in the loss of the copper(II)-binding ability of the protein in parallel with the destruction of the histidyl residues. A synthetic amino-terminal undecapeptide of alpha-fetoprotein also bound copper(II) ion. These results indicate that the histidyl residue at the amino-terminal region of alpha-fetoprotein plays an important role in the copper(II)-binding ability of the protein.