Peptidoglycan, the basic structure of the staphylococcal cell wall, is a matrix of glycan strands that are cross-linked through short peptide side chains. Many of the biological activities of staphylococcal cells can be ascribed to the peptidoglycan moiety of their cell walls. Staphylococcal peptidoglycan can be shown to be immunogenic in laboratory animals; both humoral and cellular immune responses have been noted. Sensitive techniques, such as radio- or enzyme-immunoassay, have recently shown that virtually all normal human donors have detectable peptidoglycan IgG antibodies in their serum. Peptidoglycan IgG can be transplacentally transferred. The titers of peptidoglycan antibody vary widely among healthy donors. Increased production of peptidoglycan antibodies is found in most patients with complicated S. aureus septicaemia and also in many with uncomplicated bacteremia. Nonbacteremic S. aureus infections usually do not stimulate peptidoglycan antibody production. Compared to other S. aureus products such as teichoic acid, nuclease, and alpha-toxin, peptidoglycan may be the most sensitive antigen for detecting antibody responses during staphylococcal infections. Peptidoglycan antibodies may neutralize some of the toxic effects of the staphylococcal cell wall and promote phagocytosis of the organisms. However, increased peptidoglycan antibody titers with immuno-complex disease have also been associated with longstanding infections due to S. epidermidis, Streptococci and with rheumatoid arthritis. Thus, peptidoglycan antibodies may cross-react among Gram-positive bacterial species and have detrimental effects as well.