HCC-2, a 66-amino acid residue human CC chemokine, was reported to induce chemotaxis on monocytes, T-lymphocytes, and eosinophils. The three-dimensional structure of HCC-2 has been determined by ¹H nuclear magnetic resonance (NMR) spectroscopy and restrained molecular dynamics calculations on the basis of 871 experimental restraints. The structure is well-defined, exhibiting average root-mean-square deviations of 0.58 and 0.96 Å for the backbone heavy atoms and all heavy atoms of residues 5−63, respectively. In contrast to most other chemokines, subtle structural differences impede dimer formation of HCC-2 in a concentration range of 0.1 μM to 2 mM. HCC-2, however, exhibits the same structural elements as the other chemokines, i.e., a triple-stranded antiparallel β-sheet covered by an α-helix, showing that the chemokine fold is not influenced by quaternary interactions. Structural investigations with a HCC-2 mutant prove that a third additional disulfide bond present in wild-type HCC-2 is not necessary for maintaining the relative orientation of the helix and the β-sheet.