The viridans streptococci (VS) are associated with the development of a rapidly fulminant shock syndrome in neutropenic patients. A panel of 52 VS strains isolated from the blood of neutropenic patients was used to demonstrate the ability of culture supernatants and cell walls of VS to induce release of the proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-8 from whole blood in a dose- and strain-dependent fashion. Intercellular adhesion molecule-1 was shown to be markedly up-regulated on endothelial cells after incubation with plasma from blood exposed to cell walls or culture supernatants. This up-regulation was blocked by IL-1 receptor antagonist but not neutralizing antibody against TNF-alpha. These data may help explain the pathogenesis of the viridans streptococcal shock syndrome in neutropenic patients.