Serum antibody responses to toxic shock syndrome (TSS) toxin 1 (TSST-1) and staphylococcal enterotoxins A, B, and C were determined by western blot (immunoblot) analysis of acute- and convalescent-phase paired sera from 18 TSS- and 31 non-TSS-associated Staphylococcus aureus infections. Compared with non-TSS cases, seroconversion to TSST-1 was significantly more frequent among both menstrual (5 of 8 versus 1 of 31; P less than 0.001) and nonmenstrual (3 of 10; P less than 0.05) patients. Seroconversion to staphylococcal enterotoxin A was also more frequent among both menstrual (2 of 8 versus 0 of 31; P less than 0.05) and nonmenstrual (2 of 9; P less than 0.05) TSS patients. In general, patients with TSS associated with TSST-1-positive S. aureus were more likely to seroconvert exclusively to TSST-1 (4 of 12 versus 0 of 6; P = 0.16), whereas those associated with TSST-1-negative S. aureus were more likely to seroconvert exclusively to enterotoxins (3 of 6 versus 0 of 11; P less than 0.05). Concurrent seroconversions to multiple exoproteins were more frequent among both menstrual (3 of 8; P less than 0.05) and nonmenstrual (2 of 9; P less than 0.05) TSS patients compared with persons without TSS (0 of 31). These data suggest but do not prove that enterotoxins (especially staphylococcal enterotoxin A) in addition to TSST-1 may be involved in both menstrual and nonmenstrual TSS. Furthermore, since exposure to multiple exoproteins is more likely to occur during TSS-associated than non-TSS-associated S. aureus infections, the possibility of additive or synergistic effects of these putative toxins in the pathogenesis of TSS should be further explored.