Vesicle formation in aqueous mixtures of the hydrolyzed copolymer of styrene-maleic anhydride (HSMA) and a series of single-tailed cationic surfactants (CnH2n+1N(CmH2m+1)(3)Br, n = 8, 10, 12, 16, m = 1, 2, 3, 4) was studied by fluorescence measurement, zeta potential measurement, and transmission electron microscopy. The driving forces of vesicle formation in this kind of system are attributed to the combination of electrostatic attraction and the hydrophobic interaction. Variation of the surfactant structure had a great influence on vesicle formation. A model for the conformation of the molecular packing in the vesicle membrane was suggested on the basis of XRD measurement and Chem3D simulation. Moreover, these vesicles showed superstability to aging time, to NaBr, and to ethanol.