The molar partition coefficient of the tranquilizer chlorpromazine hydrochloride (CPZ) between uniform, unilamellar phosphatidylcholine vesicles in 0.1 M phosphate buffer was measured using difference absorbance spectroscopy. The molar partition coefficient is related to the ratio between the moles of CPZ bound to the lipid vs. the moles of free CPZ in solution. Phosphatidylcholine vesicles of 1000 ? in diameter were prepared by extruding stock solutions through a polycarbonate membrane. The partition coefficient values were measured as a function of CPZ concentration, pH, and temperature. With increasing CPZ concentration, a pronounced decrease in the partition coefficient was observed. Higher values of pH resulted in an increase in the partition coefficient.The effects of temperature were studied at both above and below the main transition temperatures for each PC.The partition coefficient values were found to be higher for the liquid crystalline phases in all vesicle systems studied.