Surface proteins that bind to the Fc part of human IgA are expressed by many strains of Streptococcus pyogenes, a major human pathogen. Studies of these proteins have been complicated by their size and by their ability to bind human plasma proteins other than IgA. Here, we describe a synthetic 50- residue peptide, derived from streptococcal protein Sir22, that binds human IgA but not any of the other plasma proteins known to bind to Sir22. The peptide binds serum IgA and secretory IgA and binds IgA of both subclasses. Evidence is presented that the peptide folds correctly both in solution and when it is immobilized and that it readily renatures after denaturation. Together, these data indicate that the peptide corresponds to a protein domain that binds IgA with high specificity. This is the first report of an IgA-binding domain that retains its properties in isolated form.