Over the past decade, much progress has been made in our understanding of immunological tolerance of self-antigens and the genetic and molecular basis of T-cell recognition and activation that involves a ternary interaction of foreign or self-antigens with major histocompatibility complex molecules and T-cell antigen receptor gene products. Using this trimolecular complex as a target for immune intervention, animal models of spontaneously occurring and experimentally induced autoimmune diseases have provided opportunities for new immunomodulatory therapeutic approaches. Some of these have encouraging potential and are currently being applied in the immunotherapy of human autoimmune diseases.