Replication of Staphylococcus aureus is significantly enhanced in the presence of recombinant interleukin (IL)—1β. In this study, specific binding of IL-1β to the surface of S. aureus significantly increased growth of S. aureus in the presence of TL-1β and IL-1ra in a concentration-dependent manner. Although IL-1ra enhanced the growth of S. aureus, there was a significant reduction in IL—1β-mediated growth enhancement of S. aureus when 25-fold excess amounts of IL-1ra (in comparison with the IL-1β concentration) were present in the culture medium. Thus, IL-1β may influence the growth of S. aureus through a receptor-mediated event. By using 5 linear peptides spanning limited regions of IL-1β, the growth-promoting regions were localized to amino acid residues 118–147 and 208–240. These results build on the newly evolved concept of direct interactions between the soluble mediators of inflammation and infectious agents.