Two thymic stromal fractions previously shown to have specific enhancing effects on anatomically distinct T cell populations were tested for their capacity to induce functionally distinct T cell subsets.Parental mice were injected with either soluble thymic fraction (STF) or insoluble thymic fraction (ITF), and their lymphoid cells were harvested 11 days later. It was shown that ITF elicited a splenic corticosensitive T cell subset endowed with enhanced graft-versus-host reaction (GVHR)-inducing capacity. On the other hand, STF increased, mainly in lymph nodes, the number of corticoresistant T cells significantly less active in GVHR. Furthemore, lymphocytes from ITF-treated parental donors could become corticoresistant with reduced GVHR activity after a 1-hr in vitro incubation with STF.We have thus shown that two different elements of the thymic microenvironment could modulate the intensity of the GVHR by modifying the equilibrium between two T cell subsets. These are believed to represent two consecutive differentiation stages.