OBJECTIVE: To investigate if exposure to exotoxins results in augmented serum cytokine response of patients with Staphylococcus aureus septicemia. METHODS: Serum samples and strains from 63 patients with S. aureus septicemia were collected in a prospective study. Toxin production by strains in vitro was determined by enzyme immunoassay (EIA) or reversed passive latex agglutination (RPLA). Antibodies against the toxins and cytokine levels in serum on admission were analyzed with EIA. RESULTS: Patients infected with strains producing staphylococcal enterotoxins (SEs) A, B, C and D and/or toxic shock syndrome toxin-1 (TSST-1) in vitro (n=37) showed higher serum TNF-alpha levels than those infected with non-toxigenic strains (p=0.04). A significant titer rise against the corresponding SE and/or TSST-1 produced by the isolate (14/35), indirectly reflecting exposure to the antigen, was associated with higher TNF-alpha concentrations on admission than in those without titer rise (p=0.03). Patients with low antibody titers against SE and/or TSST-1 on admission (19/37) were found to have higher serum TNF-alpha concentrations on admission than those with elevated antibody titers on admission (p=0.03). CONCLUSION: Patients infected with toxigenic S. aureus strains produce significantly higher levels of serum TNF-alpha on admission compared to patients infected with non-toxigenic strains.