Bacterial mucopeptide is an integral part of bacterial cell walls and is therefore ubiquitous in our environment. An enhanced degree of humoral immunity has ben detected not only in patients with acute rheumatic fever (ARF), with a known recent response to streptococci, but also in patients with adult and juvenile rheumatoid arthritis (RA and JRA). Our studies confirmed this association with ARF and JRA using a precipitin system as well as a radioimmunoassay to detect IgG anti-mucopeptide antibodies. In those with adult RA, either IgM or IgA rheumatoid factors or IgM or IgA antibodies specific for mucopeptide were responsible for the increased incidence of precipitins to mucopeptide in the RA patients detected in this and other studies. No differences in the specificities of the anti-mucopeptide antibodies were noted between the various patient populations as there were no lines of partial identity or nonidentity when examined by Ouchterlony double diffusion analyses. Additionally, no differences of anti-mucopeptide antibody were observed when the sera from these same patient populations were examined employing inhibition studies utilizing N-acetylglucosamine and rhamnose.