We have used a monoclonal antibody (mAb)‐specific for murine T suppressor (Ts) cells (mAb 14‐12) to study the role of T cells in tolerance and immunoregulation. We demonstrate that mAb 14‐12 can block in vivo T, cell activity in a variety of experimental systems. It prevents the induction of Ts cells induced by i.v. injection of the water‐soluble hapten 2,4,6‐trinitrobenzene sulfonic acid, and the protein antigen bovine serum albumin. When 14‐12 mAb is given prior to the i.v. injection of Tstrinitro phenyl‐conjugated spleen cells (TNP‐SC) it blocks the induction of T, cells and sufficiently overcomes suppression so that TNP‐SC is able to induce immunity. mAb 14‐12 can convert nonresponder mice into responders for the Ir gene‐controlled response to the random terpolymer L‐glutamic acid60‐L‐alanine30‐L‐tyrosine10 (GAT), and can substitute for cyclophosphamide in overcoming a suppressor barrier in the adoptive transfer of contact sensitivity. Administration of 14‐12 mAb just prior to immunization results in the augmentation of contact sensitivity, antibody and plaque‐forming cell responses. These results demonstrate the versatility of this reagent for the study of Ts cell activity.