Vaccination protocols based on targeting of the idiotype expressed on malignant B cells have so far provided encouraging results in clinical trials. The essential requirement to induce an immune response is the inclusion of carriers to overcome T-cell tolerance. Chemical cross-linking of idiotypic protein is so far the method of choice to induce protective responses in human studies. Meanwhile, a flurry of alternative strategies to simplify vaccine production is being tested in murine model. Thanks to the advance in antibody engineering the two relevant antigenic domains of the lymphoma immunoglobulin can be assembled into an appropriate format, genetically linked to molecules that act as immunological adjuvants and directly delivered as plasmid DNA. Upon immunization, rejection of tumor cells may depend on cellular or humoral mechanisms, whose relative importance has not been entirely estimated. We have recently analyzed the specificity of anti-idiotypic antibodies induced by DNA vaccination and characterised the elements contributing to optimal anti-idiotypic responses.