Contact sensitivity (CS) reaction mediated by CD 4+8- Th 1 cells is under the control of several antigen-specific regulatory lymphocytes. Reaction is downregulated at the induction stage by T afferent suppressor T cells (Ts-aff) that prevent immunization and at the effector stage by efferent T suppressor cells (Ts-eff) that made immune Th 1 cells inoperative. Both suppressor cells are CD 4-8+ Th 1 effector cells and are protected against the suppressive action of Ts-eff cells by CD 4+8- contrasuppressor T cells (Tcs). As has been already shown there are also regulatory interactions between regulatory cells themselves and Ts-aff cells in addition to their effect on precursors of Th 1 cells, also preventing the induction of Ts-eff cells. The present experiments extend these findings and demonstrate that Ts-eff cells are also under negative control of Tcs lymphocytes. Likewise, antigen-specific factor produced by contrasuppressor T-T cell hybridoma, used in lieu of Tcs cells, impedes the activation of Ts-eff cells. In both cases regulation is aimed at the precursors of Ts-eff cells. Our experiments demonstrate that the outcome of immunization is dependent not only on the balance between immune cells and regulatory cells, but also on interactions between regulatory cells themselves.