Two different modes of antigen association with liposomes were compared for their stimulation of IgM- and IgG-producing cells in primary- and secondary-response experiments. The study was carried out on BALB/c mice using the antigen bovine serum albumin either free, encapsulated in liposomes or covalently linked to the liposomal surface. Our results indicate that, although both types of liposome association are equally efficient in potentiating the humoral response, encapsulation mainly favours IgG isotype production with little or no effect on the IgM subset, while covalent linkage stimulates the production of both IgG and IgM. Our results reconcile some apparently conflicting published data and suggest that the mode of antigen association with liposomes considerably influences the pathways by which stimulation occurs.