Group B streptococcal antigens stimulated tumor necrosis factor alpha (TNF-␣), interleukin-1 (IL-1), and IL-6 production in human blood cultures in a concentration-and time-dependent fashion. The minimal concentrations of type-specific polysaccharides, lipoteichoic acid, and group-specific polysaccharide required to produce these effects were, respectively, 0.01, 1, and 10 g/ml. Cell separation experiments indicated that monocytes were the cell type mainly responsible for cytokine production. Time course studies indicated that TNF-␣ was released before the other cytokines. TNF-␣, however, did not appear to directly induce IL-1, as shown by blockade experiments with anti-TNF-␣ antibodies. IL-6 levels were moderately but significantly decreased by anti-TNF-␣. These data indicate that several products from group B streptococci are able to directly stimulate human monocytes to release TNF-␣, IL-1, and IL-6. These findings may be clinically relevant, since proinflammatory cytokines can mediate pathophysiologic changes during sepsis.