Toxic shock syndrome toxin-1 (TSST-1) is implicated as the major exotoxin associated with menstrual toxic shock syndrome. The role of TSST-1 in nonmenstrual TSS is less certain. We examined serum IgG responses to TSST-1 in 16 nonmenstrual (9 female, 7 male) and 14 menstrual TSS patients, and in 87 women and 66 men as age-matched healthy controls, using an enzyme-linked immunosorbent assay (ELISA). Relative ELISA titers were expressed as percent activity of a mid level serum standard tested concurrently. Based on 95% confidence estimates for predicting a negative titer (20.6 +/- 8.2%) using sera in which TSST-1 specific IgG was demonstrated to be absent by western blot, 24% of control women and 9% of control men lacked TSST-1 specific IgG in the random survey (p less than 0.05, Fisher's exact test). Relative titers in acute sera of menstrual TSS women (26.2 +/- 5.2%, mean +/- S.E.), but not nonmenstrual TSS women (71.8 +/- 18.6%), were significantly lower than those of control women (78.9 +/- 7.3%, p less than 0.01, Mann-Whitney test). Acute titers from male TSS patients (37.0 +/- 15.6%) were also significantly lower than those in control men (114.6 +/- 11.0% (p less than 0.05). Antibody titers from menstrual TSS women and TSS men remained low during convalescence. Nevertheless, seroconversion to TSST-1 was demonstrated by western blot in 7 of 10 patients in whom TSST-1 positive S. aureus was isolated, but in neither of two patients without toxigenic S. aureus.(ABSTRACT TRUNCATED AT 250 WORDS)