An internal network of antibody idiotypes and anti-idiotypes has been considered important in controlling the production of antibodies reactive with exogenous antigens, and a current hypothesis proposes that some autoantibodies may be auto-anti-idiotypes. RF is often associated with bacterial (notably streptococcal) infections, as well as occurring in RA. Experimental animals immunised with streptococcal cell wall peptidoglycan-polysaccharide (PG-PS) complexes produce serum RF-like antibodies. In addition, repeated immunisation of mice with isolated IgM- or IgG-RF also produces an anti-PG-PS response, indicating that RF could act as an anti-idiotype to anti-PG-PS. Serum antibodies reactive with streptococcal PG-PS occur frequently in RA, and are notably of the IgG2 subclass.