Therapeutic usefulness of many zwitterionic drugs is hampered by their very low aqueous solubility. The purpose of this work was to investigate the effects of cyclodextrins on the solubility of the zwitterionic drug ETH-615, the role that charge might play in the cyclodextrin complexation, and the influence of polymers and ion-pairing agents on the cyclodextrin solubilization. The effects of five different beta-cyclodextrin derivatives were evaluated, i.e., the anionic beta-cyclodextrin sulfobutyl ether sodium salt and carboxymethyl-beta-cyclodextrin sodium salt, the uncharged 2-hydroxypropyl-beta-cyclodextrin and randomly methylated beta-cyclodextrin, and the cationic 2-hydroxy-3-trimethyl-ammoniopropyl-beta-cyclodextrin. The uncharged cyclodextrins had much larger solubilizing effect on ETH-615 than the charged ones. However, due to the highly polar zwitterionic structure of ETH-615 the stability constants of its cyclodextrin complexes were several orders of magnitude smaller than those commonly observed for uncharged lipophilic compounds. Cyclodextrin solubilization of ETH-615 was enhanced by water-soluble polymers and ion-pairing agents.