The Eta-1 gene specifies a secreted product of activated T cells and is associated with genetic resistance to infection by an obligate intracellular bacterium. Previous studies have suggested that eta-1 might affect the ability of macrophages to migrate to the site of bacterial infection and/or to inhibit intracellular bacterial growth. We therefore examined the interaction of eta-1 with macrophages in vitro and in vivo. We find that macrophages express approximately 10(4) eta-1 receptors/cell and each receptor has a Kd of approximately 5 x 10(-10) M. The subsequence of eta-1 containing an RGD motif is required for binding because a synthetic peptide containing the eta-1 RGD domain inhibited protein attachment to macrophages. We also found that subcutaneous inoculation of mice with eta-1 resulted in a cellular infiltrate comprised primarily of macrophages. We propose that the interaction between eta-1 and its receptor on macrophages results in a change in macrophage physiology resulting in accumulation of these cells at extravascular sites.