In order to investigate the behavior of itraconazole and benzyl alcohol in aqueous solution containing surfactants, the distribution of itraconazole and benzyl alcohol between the micellar and aqueous phases was determined and the partition of itraconazole between the hydrophilic and lipophilic moieties in micelles was measured. From these experiments, we can conclude that: (1) in aqueous surfactant solution, itraconazole mainly exists in the micellar phase; (2) the cosolvency effect of benzyl alcohol has a negligible effect on the solubility of itraconazole in aqueous solution; (3) itraconazole tends to align itself in an intermediate position (palisade layer) within the surfactant molecules forming the micelle, which may result in the destruction of the micellar structure; and (4) the precipitation of itraconazole may occur in the process of the exchange of benzyl alcohol between the aqueous and micellar phases. This is the mechanism of destabilization of colloidal drug carriers based on benzyl alcohol.