Previous studies have indicated that conventional description of drug/cyclodextrin complexes in aqueous solutions as inclusion complexes are not as unambiguous as one might think. It has been shown that in some cases drug/cyclodextrin complexes consist of a mixture of inclusion and non-inclusion complexes. Furthermore it has been shown that drug/cyclodextrin complexes can form aggregates containing up to couple of hundred complexes. In this present study beta-cyclodextrin (betaCD) solubilization of hydrocortisone is enhanced by including short-chain anionic and cationic species in the aqueous complexation medium. For example, maximum hydrocortisone solubility in pure aqueous betaCD solutions or suspensions is 2.2 mg/ml. Addition of 1% (w/v) sodium acetate to the complexation medium increases this value to 7.1 mg/ml (or over 220%). Further addition of 0.25% (w/v) hydroxypropyl methylcellulose to the medium increased the hydrocortisone solubility to over 9 mg/ml. Similar results were obtained when sodium salicylate or benzalkonium chloride were added to the complexation medium. It is also shown that cyclodextrin complexes of lipophilic compounds that have good affinity for the cyclodextrin cavity can be used to enhance cyclodextrin solubilization of drugs that have low affinity for the cavity. All these observations can be explained by formation of drug/cyclodextrin complex aggregates.