The two-site, two-step model for the interactions of chemokines with their G protein-coupled receptors involves initial binding of the chemokine N-loop/β3 region to the receptor N-terminal region and subsequent insertion of the chemokine N-terminal region into the transmembrane helical bundle of the receptor concurrent with receptor activation. Here we report experiments to test aspects of this model for chemokine receptor CCR1 and several chemokine ligands. First, we compared the chemokine binding affinities of CCR1 to those of peptides corresponding to the N-terminus of CCR1. The relatively low affinities of the peptides and the poor correlations between CCR1 and peptide affinities indicated that other regions of the receptor contribute to binding affinity. Second, we evaluated the contributions of the two interaction regions of a cognate chemokine ligand (monocyte chemoattractant protein-3; MCP-3/CCL7) using chimeras between MCP-3 and the non-cognate ligand MCP-1/CCL2. Results showed that the chemokine N-terminal region contributes significantly to binding affinity but that differences in binding affinity do not completely account for differences in receptor activation. Based on these observations, we propose an elaboration of the two-site, two-step model (the “three-step” model) in which: initial interactions of the first site result in low affinity, non-specific binding; rate-limiting engagement of the second site enables high affinity, specific binding; and subsequent conformational rearrangement gives rise to receptor activation.