We studied the influence of lipid composition on the immunomodulatory capacity of liposomal vesicles. Liposomes composed of different phosphatidylcholines (PC) and cholesterol were assayed as adjuvants for rhEGF conjugated or not to P64k from Neisseria meningitidis, and dipalmitoylphosphatidylcholine (DPPC) liposomes with or without cholesterol were tested for the encapsulation of allergens (maDer s) and sticholysin II (StII), a pore-forming protein from Stichodactyla helianthus. The immunization of mice under these conditions produced high antibody titers against rhEGF even in the absence of P64k, composed of IgG2a and IgG2b subclasses, a delayed hypersensitivity response, lymphoproliferation, and increased survival rates in mice challenged with Ehrlich's ascitic tumor. This immune response was superior when employing saturated phosphatidylcholine liposomes, as compared to unsaturated liposomes (soy bean: sPC) or Alum. Additionally, the humoral allergen-specific immune response depended on the liposomal lipid composition and on the presence of StII. No allergic responses were detected in mice immunized with cholesterol-containing liposomes; and these preparations induced the highest IgG2a/IgG1 ratio, suggesting the presence of a Th1 response pattern. These findings constitute the first reported evidence on immunomodulatory effects of StII.