Annexins are a family of proteins that bind to phospholipids and carbohydrates in a calcium-dependent manner. They are present in a variety of body fluids. Previous studies have shown that annexins have anti-inflammatory activities for lipid A of Gram-negative bacteria. The present study investigated the effect of annexins on interaction between Gram-positive bacteria and immune cells such as macrophages. Annexins I and IV bound to lipoteichoic acids which are surface molecules on Gram-positive bacteria. Binding of annexins I and IV to whole Staphylococcus aureus (S. aureus) were observed and these bindings were inhibited by lipoteichoic acid from S. aureus. Moreover, annexins I and IV suppressed the attachment of S. aureus to phorbol 12-myristate 13-acetate-treated THP-1 cells (human macrophages). These results suggest that annexins I and IV have ligand specificities toward foreign substances, and that the annexins might have some anti-inflammatory property for Gram-positive bacteria.