Low molecular weight keratin was self-crosslinked by microbial transglutaminase (mTGase) for application to wool fabric. From amino acid determination, keratin produced by the alkaline hydrolysis of wool showed requisite glutamine and lysine required for mTGase-mediated transamidation. Keratin showed less lysyl amine content after combination with mTGase as proof of self-crosslinking. Gel electrophoretic patterns provided evidence of self-crosslinking with the development of relatively higher molecular weight protein bands within 30 min after mTGase was combined with keratin at 30 degrees C. Increase in the deconvoluted amide II band from IR spectra of keratin after combination with mTGase provided further evidence of transamidation. By examining the ability of keratin to self-crosslink, past findings were elucidated whereby mTGase-mediated crosslinking imparted strength to wool and keratin controlled its dimensional stability. mTGase-catalyzed isopeptide bond formation of keratin to form monosubstituted gamma-amides of peptide-bound glutamine in epsilon-amino-(gamma-glutamyl)lysine crosslinks. This system was effective for binding wool to wool, keratin to wool, and keratin to keratin in self-crosslinking.