We studied 28 women and two men, with a median age of 20 years, who first had toxic shock syndrome between 1 February 1980 and 15 July 1981. Two of these patients died. All patients had intense myalgia, high fever (≥ 38.9 °C), hypotension or syncope, skin rash and desquamation, and abnormalities in at least three organ systems. Over half had sterile pyuria; immature granulocytic leukocytosis; coagulation abnormalities; hypocalcemia; low serum albumin and total protein concentrations; and elevations of blood urea nitrogen, alanine transaminase, bilirubin, and creatine kinase. Staphylococcus aureus was isolated from cultures from sites of soft-tissue infection in both male patients and from 13 of 19 vaginal and eight of 12 cervical cultures. All isolates produced both pyrogenic exotoxin C and enterotoxin F. All patients with a febrile, exanthematous, multisystem illness, particularly one associated with menstruation or a staphylococcal infection, should be promptly evaluated and empirically treated for toxic shock syndrome.