Interleukin-22 is a potent mediator of cellular inflammatory responses. Crystals of interleukin-22 expressed in Drosophila melanogaster S2 cells (IL-22Dm) have been grown from polyethylene glycol solutions. To obtain crystals suitable for X-ray diffraction analysis required the separation of different IL-22Dm glycosylation variants and the inclusion of the detergent cetyltrimethylammonium bromide (CTAB) in the crystallization experiments. The crystals belong to space group P21, with unit-cell parameters a = 64.88, b = 62.23, c = 139.524 Å, β = 91.35°, and diffract X-rays to 2.6 Å resolution. The crystallographic asymmetric unit contains six IL-22Dm molecules, corresponding to a solvent content of approximately 49%. © 2004 International Union of Crystallography.