G protein-coupled receptors (GPCRs) represent a large fraction of current pharmaceutical targets, and of the GPCRs, the beta(2) adrenergic receptor (beta(2)AR) is one of the most extensively studied. Previously, the X-ray crystal structure of beta(2)AR has been determined in complex with two partial inverse agonists, but the global impact of additional ligands on the structure or local impacts on the binding site are not well-understood. To assess the extent of such ligand-induced conformational differences, we determined the crystal structures of a previously described engineered beta(2)AR construct in complex with two inverse agonists: ICI 118,551 (2.8 A), a recently described compound (2.8 A) (Kolb et al, 2009), and the antagonist alprenolol (3.1 A). The structures show the same overall fold observed for the previous beta(2)AR structures and demonstrate that the ligand binding site can accommodate compounds of different chemical and pharmacological properties with only minor local structural rearrangements. All three compounds contain a hydroxy-amine motif that establishes a conserved hydrogen bond network with the receptor and chemically diverse aromatic moieties that form distinct interactions with beta(2)AR. Furthermore, receptor ligand cross-docking experiments revealed that a single beta(2)AR complex can be suitable for docking of a range of antagonists and inverse agonists but also indicate that additional ligand-receptor structures may be useful to further improve performance for in-silico docking or lead-optimization in drug design.