Cultures for Staphylococcus and sera from 434 individuals with confirmed or probable toxic shock syndrome (TSS) were studied. Three hundred forty-eight (91.6%) of the staphylococcal isolated produced TSS toxin-1 (TSST-1) alone or in combination with one or more staphylococcal enterotoxins. Isolates producing both staphylococcal enterotoxin C and TSST-1 had a higher association with nonmenstrual and fatal cases than did any other toxin combination. The sera of 284 patients with TSS were tested for antibodies to TSST-1, and 234 (82.4%) had no detectable level of antibody compared with 80 (77.7%) of 103 healthy controls having antibody levels of greater than or equal to 1:800. The sera from patients with TSS also had lower levels of antibody to staphylococcal enterotoxins A, B, and C than did the controls, a result indicating that these subjects may have an immunodeficiency that inhibits the production and/or maintenance of antibodies to the staphylococcal enterotoxins and TSST-1.