As part of a continuing program to understand better the behavior of cholesterol particles in physiological situations, an investigation of the interactions of the cholesterol surface with bile salts and alkyl surfactants was undertaken. Microelectro-phoretic techniques and adsorption experiments were employed to characterize the adsorption behavior of these agents. In contrast to the alkyl surfactants, the adsorption of bile salts on the cholesterol particle surfaces was much less than expected in the concentration ranges investigated. These results were initially surprising in light of earlier studies where bile salts were found to inhibit greatly the growth of cholesterol crystals. However, the present data are consistent with the idea that the relatively rigid bile salt molecules can adsorb only onto specific sites on the cholesterol surfaces while the more flexible alkyl surfactants can more readily interact.