A potent and structurally novel antimicrobial peptide was isolated and characterized from the stomach tissue of Bufo bufo gargarizans, an Asian toad. The 39-amino acid peptide, named buforin I, was purified to homogeneity by heparin-affinity column and reverse-phase HPLC. The amino acid sequence of buforin I was identical in 37 of 39 amino-terminal residues of Xenopus histone H2A. The buforin I showed strong antimicrobial activities in vitro against a broad-spectrum of microorganisms and was found to be more potent than magainin 2. In addition, a 21-amino acid peptide, named buforin II, which was derived from buforin I, showed more potent antimicrobial activities than buforin I. (C) 1996 Academic Press, Inc.