Considerable information concerning the serology and biochemistry of antigen-specific, T cell derived suppressor factors has been obtained using T cell hybridomas as a source of homogeneous material. Similarly, knowledge of helper T cell products and receptors is accumulating from studies of helper T cell clones and hybridomas. Our strategy for studying the mechanisms by which suppressor factors inhibit responses was to determine whether monoclonal factors could inhibit antibody responses specific for L-glutamic acid 60-L-alanine30-L-tyrosine10 (GAT) in cultures containing unprimed, splenic B cells and macrophages and GAT-specific helper T cell clones. The MHC-restricted, two chain suppressor factors, GAT-TsF2, inhibited these responses if the helper T cell clones and the suppressor factor were derived from H-2 compatible mice. Furthermore, responses were inhibited by briefly pulsing T cell clones with GAT-TsF2 in the presence of GAT indicating that suppressor factors need not be present continuously. In addition, helper T cell clones absorbed syngeneic, but not allogeneic GAT-TsF in the presence of GAT. Thus, helper T cells can serve as the cellular target of antigen-specific, MHC-restricted GAT-TsF2 and cloned helper T cells can be used as a homogeneous target population for analysis of the molecular mechanisms of T cell suppression.