The objective of this study was to determine the extent to which specific bile salt solutions and compendial dissolution media differ in their ability to wet a model surface. Solutions were examined in the concentration range of bile salts found in the gastrointestinal tract and at pH values approximating those of the stomach and small intestine. Wetting was evaluated from measurement of the surface tension of the solutions and contact angles of sessile drops on poly(methyl methacrylate). Compendial dissolution media had higher surface tensions and contact angles than bile salt solutions at 10 mM. Individual bile salts at 10 mM varied in surface tension lowering and contact angles. The contact angle-concentration profiles achieved plateau values at 2.5 mM. Dewetting was observed at low bile salt concentrations at pH 7.5. Calculated adhesion tension and interfacial tension were consistent with this behavior. The effect was attributed to the influence of the substrate surface charge on the orientation of the adsorbed bile salt molecule. Adhesion tension profiles showed that from low (<0.5 mM) to moderate (2 mM) concentrations preferential bile salt adsorption to the liquid-vapor interface occurred, but at higher values (>2 mM) the preference shifted toward the solid-liquid interface. These results have implications in the design of physiologically based dissolution media.