AbstractThe induction of tolerance to the 2,4,6‐trinitrophenyl (TNP) hapten has been studied in a system utilizing haptenated syngeneic lymphoid cells. Specific depression of the direct and indirect plaque‐forming cell (PFC) responses to TNP‐protein conjugates was regularly achieved by pretreatment of Lewis rats with 1 × 107trinitrophenylated spleen cells or TNP lymph node cells. Very low numbers of haptenated lymphocytes were active since tolerance could be induced in vivo with as few as 105−106TNP spleen cells (SC). SC exposed to as little as 10–100 μg of the reactive hapten, trinitrobenzene sulfonic acid, were effective tolerogens in this system. Tolerance induced with 107hapten‐ated spleen cells persisted for at least 4 weeks. Viable intact cells did not seem to be required in this system since the cell‐free supernatants from TNP‐SC cultured for 24 h were also active. In addition, significant depression of an ongoing immune response could also be imposed by haptenated isologous lymphoid cells. Moderate suppression of the “hapten‐specific” delayed hypersensitivity response (measured by the accumulation of51Cr‐labeled bone marrow cells) was also achieved with TNP‐SC. These results suggest that haptenated isologous lymphoid cells are potent tolerogenic conjugates capable of inducing tolerance affecting antibody formation and delayed hypersensitivity. However, since we and others have shown that TNP‐SC do not adversely affect the generation of hapten‐specific cytotoxic T cells, it is postulated that there is a differential recognition of, or response to, hapten‐modified self‐carriers by functionally