Erythrocytes have long been appreciated as transporters and exchangers of O2 and CO2 between the lungs and the tissues. Here we examine the role of erythrocytes as potential mediators of inflammatory processes by assessing their ability to bind to a number of inflammatory peptides of the chemokine (for chemoattractant cytokine) superfamily. Radiolabeled chemokines of either the C-X-C (IL-8, MGSA/gro, NAP-2) or C-C (RANTES, MCP-1) class bind reversibly to red cell surface receptors numbering 1000-9000 sites/cell with a Kd of approximately 5 nM. In contrast to what is seen for chemokine binding to target inflammatory cells, chemokines of either class displace heterologous chemokines, indicating that the proteins are competing for a promiscuous receptor. Chemical cross-linking with radiolabeled chemokines reveals a 30-38-kilodalton protein on the red cell surface, and cross-linking is inhibited in the presence of heterologous unlabeled chemokines. These data show that red blood cells possess a multispecific receptor for the newly identified chemokine superfamily of inflammatory cytokines, and thus the red cell may play a novel role as a regulator of inflammatory processes.