Current emphasis on risk factors associated with established vaccines and pressing needs for vaccines against certain viral transmitted diseases have stimulated the search for new conceptual and practical approaches to vaccine production. Among these developments, the idiotope vaccine method has produced promising results. In this review the basic and conceptual principles for idiotype vaccine design are discussed. A novel approach for identifying idiotopic structures in the three dimensional structure of internal idiotope antigens is developed. The method is based on the relationship of the immune response with the evolutionary variation and diversity of the immunoglobulin family. Idiotopic structures are found in specialized topographic regions on the surface of the immunoglobulin molecule. The knowledge of these idiotope domains will facilitate the synthesis of idiotope expressing peptides and the computer modeling of the three dimensional structure of internal idiotope antigens. Finally, the existing evidence for successful application of the idiotope vaccine method is summarized and new disease groups are identified which could benefit from the development of idiotope vaccines.