Protein G, a bacterial cell wall protein isolated from group G Streptococci, binds to mammalian IgGs mainly through Fc regions. Native protein G has 3 IgG binding domains and also sites for albumin and cell-surface binding. The latter have been eliminated from recombinant protein G to reduce nonspecific binding. Although protein G has very similar tertiary structures to protein A, their amino acid compositions differ significantly, resulting in different binding characteristics. Protein G can be used for purification of mammalian monoclonal and polyclonal IgGs that do not bind well to protein A. Protein G has greater affinity than protein A for most mammalian IgGs, especially for certain subclasses including human IgG3, mouse IgG1 and rat IgG2a. Unlike protein A, protein G does not bind to human IgM, IgD and IgA.