Streptococcal toxic shock syndrome (strep TSS) with associated necrotizing fasciitis is a rapidly progressive process that kills 30-60% of patients in 72-96 h. Violaceous bullae, hypotension, fever, and evidence of organ failure are late clinical manifestations. Thus, the challenge to clinicians is to make an early diagnosis and to intervene with aggressive fluid replacement, emergent surgical debridement, and general supportive measures. Superantigens such as pyrogenic exotoxin A interact with monocytes and T lymphocytes in unique ways, resulting in T-cell proliferation and watershed production of monokines (e.g. tumor necrosis factor alpha, interleukin 1, interleukin 6), and lymphokines (e.g. tumor necrosis factor beta, interleukin 2, and gamma-interferon). Penicillin, though efficacious in mild Streptococcus pyogenes infection, is less effective in severe infections because of its short postantibiotic effect, inoculum effect, and reduced activity against stationary-phase organisms. Emerging treatments for strep TSS include clindamycin and intravenous gamma-globulin.