[en] Proteins can use aromatic side-chains to stabilize bound cationic ligands through cation-π interactions. The first example of the reciprocal process, termed π-cation, is reported in which a cationic protein side-chain stabilizes a neutral aromatic ligand. Site-directed mutagenesis revealed that an arginine side-chain located in the deep binding pocket of a monoclonal antibody (4D5) is essential for binding the neutral polynuclear aromatic hydrocarbon benzo[a]pyrene. This Arg was very likely selected for in the primary response, furhter underscoring the importance of the π-cation interaction for ligand binding, which should be considered in protein analysis and design when ligands include aromatic groups