Protamines (salmine prepared from sperm DNA of salmon and clupeine from herring sperm), which are basic peptides rich in arginine, were found to inhibit the proteolytic activity of arginine-specific cysteine protease (RC-protease) from Porphyromonas gingivalis. Lineweaver-Burk plot analysis revealed that the protamines competitively inhibited proteolytic activity with cleavage of benzoyl-L-arginine-p-nitroanilide, a synthetic substrate of RC-protease. Furthermore, the protamines were capable of binding strongly to P. gingivalis fimbriae and inhibited fimbrial interaction with immobilized fibronectin. These results clearly show that protamines are potent inhibitors of the proteolytic and adhesive activities of P. gingivalis.