Lipoteichoic acid (LTA), a component of the cell wall of most gram-positive bacteria, has been shown to play a significant role in the initiation and progression of bacterial infection. However, little is known of its position in the cytokine network involved in the induction and perpetuation of inflammation. In this study, we assessed whether the macrophage activating and chemotactic cytokine macrophage inflammatory protein-1 alpha (MIP-1 alpha) was expressed in the setting of localized gram-positive infection. Furthermore, we determined whether LTA purified from either Staphylococcus aureus or Streptococcus pyogenes could induce the expression of MIP-1 alpha mRNA and protein from human blood monocytes. Immunohistochemical staining of human endocardial samples obtained from patients with acute S. aureus endocarditis revealed cell-associated MIP-1 alpha expression by neutrophils, macrophages, and fibroblasts. Treatment of human peripheral blood monocytes in vitro with LTA isolated from either S. aureus or S. pyogenes resulted in both the time- and dose-dependent expression of MIP-1 alpha mRNA. Similarly, staphylococcal and streptococcal LTA induced the dose-dependent production of MIP-1 alpha protein after 24 h in culture. These studies suggest that LTA may play an important role in triggering the recruitment and activation of leukocytes that characterizes the host response to gram-positive bacterial invasion.