Anecdotal reports suggest an association between the use of nonsteroidal antiinflammatory drugs (NSAIDs) and the progression of invasive group A streptococcal infections to shock and multiorgan failure. There is a biochemical rationale that could support this theory. Though NSAIDs are frequently used to relieve pain or reduce fever, they also attenuate granulocyte functions such as chemotaxis, phagocytosis, and bacterial killing. In addition, findings in recent studies involving human volunteers injected with endotoxin suggest that pretreatment with NSAIDs enhances production of tumor necrosis factor, which leads to higher blood levels of this cytokine, probably by preventing feedback inhibition by prostaglandin E2. Thus, NSAIDs may contribute to the sudden onset of shock, organ failure, and aggressive infection by inhibiting neutrophil function, augmenting cytokine production, and attenuating the cardinal manifestations of inflammation.