On the basis of the datum that the level of Zn-alpha 2-glycoprotein (Zn alpha 2gp) in human seminal plasma was about 6-times higher than that in adult serum, Zn alpha 2gp was purified from fresh human seminal plasma approx. 70-fold with 60% yield over seminal plasma by DEAE-Sephacel, Zn-chelate Sepharose 4B and DEAE-5PW column chromatographies. The molecular weight of seminal plasma Zn alpha 2gp was 50,000 on Superose column chromatography, and 40,500 and 41,500 on SDS-polyacrylamide gel electrophoresis in the absence and presence of beta-mercaptoethanol, respectively. Plasma Zn alpha 2gp is a glycoprotein, while the protein from seminal plasma does not contain carbohydrate. The amino acid sequence of the first 17 residues of seminal plasma Zn alpha 2gp was Glu-Asn-Gln-Asp-Gly-Asn-Tyr-Ser-Leu-Thr-Tyr-Ile-Tyr-Thr-Gly-Leu-Ser. This sequence was completely identical with the amino acid residues from Glu-2 to Ser-18 in the N-terminal amino acid sequence of plasma Zn alpha 2gp. These data suggest that both Zn alpha 2gps in plasma and seminal plasma may be expressed from one gene, but their posttranslational modifications are different.