The crystal structure of recombinant human interleukin 10 (rhIL-10) has been determined by X-ray crystallography at 2.0 Å resolution. Interleukin 10 is a dimer composed of identical polypeptide chains related by a 2-fold axis. The molecule is predominantly α-helical. The main-chain fold resembles that of interferon γ (IFN-γ) in which the structural integrity of each domain is dependent on the intertwining of helices from each peptide chain. Comparison of rhIL-10 and IFN-γ reveals differences in helix lengths and orientations of the 2-fold related domains. Interleukin 10 and IFN-γ contain several conserved residues in their internal cores which suggest a possible “fingerprint” for detection of other members of this fold. © 1995, American Chemical Society. All rights reserved.