Bile salt mixed micelles play an important role in the emulsification, solubilization, and absorption of cholesterol, fats, and lipid-soluble vitamins. Studies have also revealed the importance of wetting and solubilization of drugs by the bile salts; however, the capacity and specificity of bile salt simple and mixed micelles for solubilization are still undefined. Thus, in this study the aqueous solubility and the extent of solubilization in bile salt micellar solutions of a series of steroids were determined. The melting point and enthalpy of fusion were measured to determine the ideal mole fraction solubility of each steroid. From the ideal mole fraction solubility and the observed solubility of each steroid, the activity coefficient of each steroid in solution was calculated with respect to the supercooled pure liquid as the standard state. In aqueous solution, the activity coefficients decreased with increasing number of hydroxyl groups on the steroids. This trend also occurred in the bile salt solutions, although the values of the activity coefficients were smaller by about three orders of magnitude. The stereochemical position of the hydroxyl groups influenced the rank order of the activity coefficients in the aqueous and micellar solutions. Incorporation of a fluoro or methyl group resulted in an increase in the activity coefficient, whereas aromatization of the A ring of the steroid frame markedly decreased the activity coefficient. The results for the aqueous solubility are consistent with the expected interaction of the functional groups with the polar environment. The relatively small activity coefficients observed with the micellar solutions result from the nonpolar environment of the aggregates. However, the similarity of the relationship between the activity coefficient and the number of hydroxyl groups in the aqueous and micellar solutions indicates the importance of polar interactions for solubilization. These results may provide new insight into the solubilization of steroids by bile salt micellar solutions and may provide a basis for predicting solubilization of other compounds by bile salt aggregates.