T cells were obtained from mice immunized to keyhole limpet hemocyanin (KLH) and tested in culture for their proliferation to KLH or to concanavalin A. The T-cell proliferation to KLH depended on the presence of Ia-bearing macrophages. This was shown only after extensive manipulations of T cells depleting accessory cells by adherence to dishes and passage through nylon-wool columns. The macrophage dependency required homology with macrophages from strains of mice sharing the left side of H-2. The macrophage dependency was not bypassed by conditioned media from macrophages. In contrast, the proliferative response to concanavalin A, which was also macrophage dependent, showed no H-2 restriction and could be replaced by a macrophage-conditioned medium. Nonadherent spleen cells, extensively devoid of macrophages, could substitute for macrophages but at a hundredfold excess. Cells isolated in the fluorescence-activated cell sorter with anti-Ig reagents also showed an antigen-presenting function. We raise the question whether our results imply an antigen-presenting function of B cells.