<jats:p>In response to epidermal injury, <jats:italic>Parasilurus asotus</jats:italic>, a catfish, secreted a strong antimicrobial peptide into the epithelial mucosal layer. The molecular mass of the antimicrobial peptide, named parasin I, was 2000.4 Da, as determined by matrix‐associated laser desorption ionization mass spectrometry. The complete amino acid sequence of parasin I, which was determined by automated Edman degradation, was Lys‐Gly‐Arg‐Gly‐Lys‐Gln‐Gly‐Gly‐Lys‐Val‐Arg‐Ala‐Lys‐Ala‐Lys‐Thr‐Arg‐Ser‐Ser. Eighteen of the 19 residues in parasin I were identical to the N‐terminal of buforin I, a 39‐residue antimicrobial peptide derived from the N‐terminal of toad histone H2A [Kim et al. (1996) Biochem. Biophys. Res. Commun. 229, 381–387], which implies that parasin I was cleaved off from the N‐terminal of catfish histone H2A. Parasin I showed strong antimicrobial activity, about 12–100 times more potent than magainin 2, against a wide spectrum of microorganisms, without any hemolytic activity. Circular dichroism spectra of parasin I indicated a structural content of 11% α‐helix, 33% β‐sheet, and 56% random coils. The β‐sheet axial projection diagram of parasin I showed an amphipathic structure. Our results indicate that the catfish may produce parasin I from its histone H2A by a specific protease upon injury to protect against invasion by microorganisms.