Staphylococcal enterotoxin F (SEF) has previously been shown to be a marker for toxic-shock syndrome (TSS)-associated strains of Staphylococcus aureus, whereas the serologic absence of antibody to SEF (anti-SEF) has been shown to be a marker for susceptibility of persons to TSS. In this study, anti-SEF was measured by radioimmunoassay in 689 banked sera obtained from Wisconsin residents during 1960, 1970, and 1980. The prevalence of anti-SEF as estimated by logistic regression analysis was 47%, 58%, 70%, 88%, 96%, and 99% at ages one, five, 10, 20, 30, and 50 years, respectively. Evidence for the transplacental transfer of anti-SEF is also presented. Despite the reported increased incidence of TSS occurring during the past five years, with a preponderance of cases occurring among women, no significant differences in the prevalence of anti-SEF were noted between sexes or longitudinally between the years 1960, 1970, and 1980. These data enhance our understanding of the epidemiology of TSS and further identify the population that may be susceptible to TSS.