Extruded vesicles, which are often used as models for living cells, can change their morphology when they are diluted into a hyperosmotic medium. Different morphological changes were observed with extruded dioctadecyldimethylammonium chloride (DODAC) vesicles after dilution with a nonionic (sucrose) and ionic (CaCl2) osmotic agent above and below the gel-to-liquid crystalline transition temperature. By means of turbidimetry, dynamic light scattering, and cryo-transmission electron microscopy, it was seen that the vesicles only deflated when they were in the gel state, whereas in the liquid crystalline state, an ionic osmotic agent could induce twinning of the vesicles, reminiscent to endocytosis. The latter could occur as a result of the combined effects of reduced repulsion, local dehydration, and reduced bending rigidity induced by the ionic agent.