Aims: To investigate the association between toxin-producing staphylococci, symptom expression, and changes in urinary excretion of metabolites in temporomandibular disorder (TMD) patients and age- and sex-matched control subjects. Methods: Twenty-nine patients defined by the research diagnostic criteria/TMD as having Type 1a muscle pain (TMD1A), and 34 age- and sex-matched control subjects were assessed for the carriage of staphylococcal species, staphylococcal toxin production, expression of symptoms, and changes in urinary excretion of amino and organic acids. Results: TMD1A patients had an increased incidence of carriage of toxin-producing coagulase-negative staphylococcus (MDT-CoNS, P .004), which produced increased levels of δ-like membrane-damaging toxins. The TMD1A patients also had a reduction in the incidence of carriage of Staphylococcus aureus (P .02). Increased incidence of MDTCoNS was positively associated with increased pain intensity as assessed by a visual analog scale (P .001). Odds ratio analysis revealed a 9.2-fold increase in MDT-CoNS recovery from the nose of TMD1A patients compared with the control subjects (odds ratio = 9.2, > 95% confidence limits: 2.3 to 37.5, P .001). Increases in the carriage incidence of MDT-CoNS were also associated with increases in the urinary tyrosine:leucine ratio (P .004), which represents a change in the balance of proteolysis and protein synthesis. The toxin production by these CoNS species was also associated with an increased urinary excretion of glutamic acid (P .03). Conclusion: These data suggest that an increased colonization of MDT-CoNS on skin and mucosal membranes was associated with changed proteolysis, increased pain intensity, and an increase in excitatory amino acids consistent with events associated with the development of chronic orofacial muscle pain in TMD patients. Keywords: facial pain, metabolism, microbiology, temporomandibular disorders, staphylococcus pathogenicity, staphylococcal haemolysins, staphylococcal toxicity