Toxic shock syndrome-associated staphylococcal and streptococcal exotoxins were tested for an ability to induce the production of tumor necrosis factor (TNF). Staphylococcal enterotoxins B and C1, along with streptococcal pyrogenic exotoxin A, all induced TNF production in a dose-dependent manner, with production peaking on the average at 3 days but continuing over the 6 days tested. This time course of exotoxin-induced TNF production contrasts with the 1-day peak-2-day duration observed with endotoxin as the stimulus and may be significant to development of toxic shock syndrome.