Phosphatidylcholine (PC)-cholesterol (0-30 mol%) unilamellar vesicles of several sizes (20-600 nm) were prepared in buffer (pH 7.4) solutions by sonication or extrusion methods. The vesicle size was measured by a dynamic light-scattering method. Absorption spectra of chlorpromazine (CPZ) and triflupromazine (TFZ) in the presence of these vesicles showed a bathochromic shift according to the increase in vesicle concentration, but the counterbalance of the baseline was incomplete due to the intensive light scattering by the vesicles; thus, no isosbestic point could be observed. In the second-derivative spectra, the residual background signal effects were eliminated and three derivative isosbestic points were clearly observed for both drugs. The derivative intensity change (Delta D) induced by the addition of the vesicles was measured at the lambda(max) of each drug. From the relationship between the Delta D value and the Lipid concentration the partition coefficients (K-p) of CPZ and TFZ between these vesicles and water (buffer) were calculated. The results revealed that the vesicle size (20-600 nm) and preparation method do not affect the K-p values, and although the incorporation of cholesterol into the PC bilayers induces a decrease of the K-p values, the vesicle size also did not affect the K-p values in vesicles of the same cholesterol content,