A single-site human growth hormone mutant (hGH[G120R]), which inhibits receptor dimerization, was used to produce single crystals, suitable for high-resolution diffraction studies, of 1:1 complexes with the ligand-binding domain of the growth hormone receptor (hGHbp) and of the prolactin receptor (hPRLbp). Crystals of the hGH[G120R]-hGHbp complex are in space group P4(1)2(1)2 or P4(3)2(1)2 with a = 67.7 A, c = 228.0 A, and diffract to at least 2.2 A. Crystals of the complex between hGH[G120R] and hPRLbp are in space group P2(1)2(1)2 with a = 154.0 A, b = 68.4 A, c = 42.9 A, and diffract to at least 2.8 A. The structures of these two complexes will shed light on the early events in receptor activation, and provide the basis for an analysis of receptor specificity of growth hormone and prolactin.