The surface phenotypes and differentiative history of specific helper-effector (HE) and specific feedback suppression-inducer (FBSI) cell sets were further defined in reference to the Qa-1 and I-J marker systems by culture of selected sets of cortisone-resistant nylon-purified thymocytes with antigen on primed macrophages. The generation of Ly-1:HE and Ly-1:FBSI cell sets required, in each case, two initiating sets: a precursor set and a differentiation-inducing set. Precursor sets were distinguished from inducer sets by genetic markers. Accordingly, HE cells, phenotype Ly-1:Qa-1-:I-J-, differentiated from Ly-123:Qa-1- cells in the presence of Ly-1:Qa-1+:I-J+ inducer cells; and FBSI cells, phenotype Ly-1:Qa-1+:I-J+, differentiated from Ly-123:Qa-1- in the presence of Ly-1:Qa-1+:I-J+ inducer cells. The Ly-123:Qa-1-precursors of HE and FBSI cells have been distinguished from one another previously but there is as yet no evidence whether differentiation of these precursor sets requires the same or different Ly-1:Qa-1+:I-J+ inducer sets.