The mechanism by which I-J restrictions were imposed on second-order suppressor cells (Ts2) was analyzed. The induction of Ts2 cells requires presentation of an inducer suppressor factor by a specialized population of factor-presenting cells. The I-J phenotype of this factor-presenting population controls the H-2 restriction of the Ts2 cells. The splenic cells responsible for presenting inducer factor appear to be of macrophage or dendritic cell lineage. Several homologies exist between the mechanism responsible for the induction of H-2-restricted suppressor and helper T cells. Thus, the I region products on specialized presenting cells determine the specificity and genetic restrictions of the T cell. In an H-2 heterozygous F1 animal, two distinct populations of cells can be induced, one specific for each parental H-2 heplotype. Furthermore, the data suggest that the suppressor cells also bear receptors for self H-2 products. The ramifications of these observations for the suppressor cell cascade are discussed.