Abstract Syngeneic proliferative response of splenic T cells against monolayers of epidermal basal cells (EBC) was obtained with C57BL/6 and DBA/2 mice. Optimal response, as assessed by [ 3H]thymidine uptake, occurred on the 6th day of coculture. The level of [ 3H]thymidine uptake by unseparated spleen cells was lower than by fractionated T cells from C57BL/6 mice, and null for DBA/2 mice. It was not significantly different when lymphocytes were cocultured with syngeneic or allogeneic epidermal cells. Ia antigens did not appear to be involved in the syngeneic response, since it was not prevented by pretreating stimulator monolayers with monoclonal anti-Ia k antibody or by adding this antibody directly to the cultures. When the proliferative responses of separated Lyt 1 + and Lyt 2 + cell subsets were compared, the prominent role of Lyt 1 + cells was demonstrated. Enhancement of the T-cell reactivity by eliminating Lyt 2 + cells and suppression of the response of a constant number of Lyt 1 + cells by adding Lyt 2 + cells suggested that Lyt 2 + cells could suppress and modulate the Lyt 1 + cell proliferation.