It is well established that most G protein-coupled receptors are able to form homo-and heterodimers, although the functional consequences of this process often remain unclear. CCR5 is a chemokine receptor that plays an important role in inflammatory diseases and acts as a major coreceptor for human immunodeficiency viruses. CCR5 was previously shown to homodimerize and heterodimerize with CCR2b, a closely related receptor. In the present study, we have analyzed the functional consequences of this dimerization process, in terms of ligand binding, stimulation of intracellular cascades, and internalization. Bioluminescence resonance energy transfer and coimmunoprecipitation assays demonstrated that CCR5 and CCR2b heterodimerize with the same efficiency as they homodimerize. In contrast to what has been reported previously, no cooperative signaling was observed after costimulation of the two receptors by their respective ligands. However, we observed that CCR5-specific ligands that are unable to compete for monocyte chemoattractant protein (MCP-1) binding on cells expressing CCR2b alone efficiently prevented MCP-1 binding when CCR5 and CCR2b were coexpressed. The extent of this cross-competition was correlated with the amount of CCR5 expressed in cells, as determined by fluorescence-activated cell sorting analysis. Similar observations were made for the CCR2b-selective ligand MCP-1 that competed efficiently for macrophage inflammatory protein-1␤ binding on cells expressing both receptors. Internalization assays did not allow us to demonstrate cointernalization of the receptors in response to agonist stimulation. Together, our observations suggest that CCR5 and CCR2b form homo-and heterodimers with similar efficiencies and that a receptor dimer can only bind a single chemokine.