Several inbred strains of Syrian hamsters have been immunized by skin painting with highly reactive haptens. Classical contact hypersensitivity has been assayed by the ear swelling response: the response is hapten-specific, exaggerated after re-immunization with the original hapten, and can be transferred adoptively to naive syngeneic hamsters with viable lymphoid cells, suggesting that contact hypersensitivity is mediated in hamsters by T lymphocytes. Moreover, skin painting with hapten induces significant serum titers of anti-hapten antibodies, indicating that antigen-specific B lymphocytes are also activated. Hamsters can be rendered unresponsive to these same haptens by conventional methods: 1) i.v. inoculation of the soluble hapten sulfonate or 2) inoculation of hapten-derivatized syngeneic lymphoid cells. Hamsters treated with these "tolerizing" maneuvers develop profound hapten-specific unresponsiveness that can be adoptively transferred to naive recipients with living lymphoid cells. "Unresponsive" animals, however, make strong anti-hapten antibody responses that rival the humoral immune responses found after skin sensitization. The data suggest that an active process is involved in the induction and maintenance of the unresponsive state, but responsibility can not be assigned firmly to putative suppressor T cells or to an antibody-mediated B suppressor modality.