B and T lymphocytes with reactivity against major histocompatibility antigens are known to express this immune potential via a display on the outer surface of antigen-specific, idiotypic receptors. Here, we show that anti-idiotypic antibodies directed against such receptors may serve as specific triggering agents of the idiotype-positive lymphocytes in the physical absence of foreign histocompatibility antigens. This was shown in vitro using normal or immune spleen T cells where anti-idiotypic antibodies would lead to the selective proliferation and development of antigen-specific cytolytic T cells as determined by short-time 51Cr release assays. Furthermore, purified anti-idiotypic antibodies in adjuvant administered in vivo to normal syngeneic animals could be shown to lead to production of high titers of specific alloantibodies. The present experiments were in most cases carried out using auto-anti-idiotypic antibodies as triggering agents. The present results thus lend further support to the concept that idiotype-anti-idiotype reactions may be normal parts of conventional immune processes with either stimulatory or inhibitory consequences, depending upon the prevailing conditions.