A number of rat monoclonal antibodies of the IgG2b subclass have been used to deplete mice of T lymphocyte subsets. It has been possible to produce long-term depletion where antibodies are administered to mice thymectomized in their adult life, or short-term depletion in euthymic animals. It is therefore feasible to ablate a T lymphocyte subpopulation at any stage in the course of an immune response and to examine in detail the role of a particular subset in the induction or effector phases of that response. We have used such ablative procedures to define the T cell subsets which participate in graft rejection, graft-versus-host disease, antigenic competition and antiviral and anti-self immunity and have attempted to exploit such knowledge to establish immunological tolerance in an adult animal.