The X-ray crystal and molecular structures of the three benzodiazepine (BZD) receptor ligands are presented and the electronic character of inverse agonist ligands is probed through molecular orbital calculations. Two of the ligands have a 6-benzylamino substituent: 6-benzylamino-β-carboline-3-carboxylic acid methyl ester,1, which is a high affinity antagonist with IC50 = 10 nM, and 6-benzylamino-β-carboline,2, which is a moderate affinity inverse agonist with IC50 = 106 nM. The third compound, 3-ethoxy-β-carboline hydrochloride,3, displays partial inverse agonist activity with an IC50of 24 nM. Intermolecular interactions, including extensive hydrogen bonding involving both the pyridyl nitrogen atom and the indole N—H as well as π stacking of aromatic rings, are characteristic of β-carbolines and are found in these three structures. In addition, two of these compounds are protonated in the crystalline state, thereby providing a model for interactions in the absence of the 3-carboxylic acid ester function. Electronic calculations show that (1) the partial inverse agonist ligand has the highest charge on the N(2) atom and (2) high affinity β-carbolines possess two neighboring sites that have high electrostatic attraction for a hydrogen atom in an intermolecular interaction. These findings suggest that modifications to the 3-position side chain to enhance the charge on the pyridyl N atom and provide a hydrogen bond acceptor site will facilitate the development ofpartialinverse agonist ligands.Keywords: β-carbolines, benzodiazepine receptor, crystallography, structure–activity relationships.