This chapter discusses GAT antigen-specific suppressor factors. It has employed the synthetic polypeptide antigen GAT. The capacity of various strains of mice to make antibody following antigenic challenge with this polypeptide is under the genetic control of immune response or Ir genes which are mapped to the I-A subregion of the I-region locus located in the murine MHC. In the case of GAT, mice can be divided into two groups based on their H-2 haplotype and their capacity to make antibody following exposure to GAT. With both GAT and with a related synthetic polypeptide GT it is highlighted that there are at least two suppressor cell classes, Ts1 and Ts2. Following antigen stimulation, Ts-1 is activated and releases TsF-1, a single-chain polypeptide which suppresses across H-2 strain barriers. This TsF1 acts by stimulating a Ts2 cell to release TsF2 which is composed of a two-chain, disulfide-linked heterodimer which will only suppress the response to GAT or GT in a histocompatible strain. The chapter further describes the production and purification of GAT-TsF. © 1985, Elsevier Inc. All rights reserved.