The subcellular components of type III group B streptococci (GBS) that contribute to the host inflammatory response were determined by measuring production of the proinflammatory cytokine interleukin (IL)-6 by cord blood monocytes. Monocytes were stimulated with encapsulated (COH1) or unencapsulated (COH1-13) whole type III GBS or with purified GBS components, including type III capsular polysaccharide (III-PS), group B antigen (GB-Ag), lipoteichoic acid (LTA), or Escherichia coli lipopolysaccharide. Monocytes exposed to COH1 and COH1-13 released similar amounts of IL-6. GBS III-PS, GB-Ag, and LTA each induced IL-6. However, IL-6 release by monocytes was significantly greater after stimulation by GB-Ag than by III-PS or LTA (P < .05). Sera from 16 neonates with systemic GBS disease had IL-6 levels of 8 pg/mL to 4.28 ng/mL. GB-Ag is a potent inducer of IL-6 and may play an important role in tissue inflammation during GBS infection.