We have analyzed the genetic control of susceptibility to suppression by 1-J+, suppressor-T-cell derived factors (TsF) specific for the synthetic polymer L-glutamic acid50-L-tyrosine50 (GT). GT-TsF activity was measured as specific inhibition of proliferative responses to GT developed in cultures of lymph-node T cells from mice primed with GT complexed to methylated bovine serum albumin (GT-MBSA). These experiments demonstrated that there is no MHC-encoded genetic restriction between donors and recipients of GT-TsF in suppression of proliferative responses. We have also confirmed the observations that mice of the H-2b, H-2d, and H-2khaplotypes can produce GT-TsF, whereas H-2amice do not, and that H-2b, H-2d, and H-2kmice are sensitive to GT-TsF from all producer strains, whereas H-2bmice are not sensitive to GT-TsF from any strain. Analysis of the effect of GT-TsF on responses by mice bearing recombinant haplotypes suggests that at least two genes are required for susceptibility to GT-TsF and that these genes show coupled complementation. © 1981 Springer-Verlag GmbH & Co KG.