To determine the risk factors associated with toxic-shock syndrome (TSS) in menstruating women, we conducted a retrospective telephone study of 52 cases and 52 age-matched and sex-matched controls. Fifty-two cases and 44 controls used tampons (P < 0.02). Moreover, in case-control pairs in which both women used tampons, cases were more likely than controls to use tampons throughout menstruation (42 of 44 vs. 34 of 44, respectively; P < 0.05). There were no significant differences in brand of tampon used, degree of absorbency specified on label, frequency of tampon change, type of contraceptive used, frequency of sexual intercourse, or sexual intercourse during menstruation. Fourteen of 44 cases had one or more definite or probable recurrences during a subsequent menstrual period. In a separate study, Staphylococcus aureus was isolated from 62 of 64 women with TSS and from seven of 71 vaginal cultures obtained from healthy controls (P < 0.001).