We present a new protein from X. laevis skin termed "frog integumentary mucin B.1" (FIM-B.1) with a general structure similar to FIM-A.1 (formerly "spasmolysin"). The central region consisting of tandem repeats of 11 amino acid residues is probably a target for extensive O-glycosylation, whereas the C-terminal cysteine-rich domain shows pronounced homology with the C1-C2 domains and the C-terminal end of von Willebrand factor. Furthermore, we describe homology with antistasin, an anticoagulant peptide from a leech. We also discuss some implications concerning the evolutionary origin of von Willebrand factor. In situ hybridization studies revealed the expression of FIM-B.1 exclusively in mucous glands of the skin. This is comparable with FIM-A.1 but is in contrast to all other physiologically active peptides, which are synthesized in granular glands.