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"Cystic fibrosis protein" (CFP), a minor serum protein marker of the cystic fibrosis allele, was isolated from serum from patients with cystic fibrosis by use of the "FPLC" high-resolution chromatography system and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. CFP currently is characterized by its isoelectric point (8.4) on isoelectric focusing. However, after the first purification steps, we identified the protein, which was present in a very low concentration, by the immunosorbent assay of Hayward et al. (J Immunol Methods 1986;91:117-22), by virtue of its immunological relationship with the "CF antigen," a protein characterized in granulocytes by these same authors [Nature (London) 1985;315:513-5]. CFP, a protein of low molecular mass, about 14 kDa, appears to be strongly associated with IgG in serum. Using the same procedure with control serum permits us to assume that CFP normally is present in serum in trace amounts.