The complex crystal of granulocyte colony-stimulating factor (G-CSF) and its soluble receptor, the principal ligand-binding region, was obtained by a vapor-diffusion method using ammonium sulfate as a precipitant. The addition of 1, 4-dioxane was effective to grow the crystals to sufficient sizes for X-ray diffraction. The cryoprotection was essential to collect diffraction data at an atomic resolution. The crystal form changed from I-tetragonal to P-tetragonal, depending upon the difference of the salt concentration of the cryoprotectant. The crystal structure revealed that the two sets of a 1 : 1 complex between receptor and G-CSF form a 2 : 2 complex with a non-crystallographic pseudo-two-fold axis. This first structural view of a complex between type 1 cytokine and its receptor presents a new molecular basis for cytokine-receptor recognition.