Sublethal irradiation of the murine thymus has been a useful tool for depleting the thymus of dividing immature thymocyte subsets, to sequence thymocyte differentiation events occurring from radiation-resistant precursors. This massive reduction in thymocytes also represents a model in which the bidirectional interplay between the thymic stromal cells and lymphocytes can be investigated. The purpose of this study was thus twofold: to precisely map the initiation of thymopoiesis as a prelude to assessing the effects of injected mAb to novel thymic antigens; and to use a panel of mAbs to determine the alterations in the thymic stroma during the T-cell depletion and reconstitution phases. The striking finding from this study was that following T-cell depletion, there was a marked upregu- lation of specific stromal antigens, which retracted with the reappearance of T cells. Thus, following sublethal irradiation, there are modifications in the thymic microenvironment that may be necessary to support renewed thymopoiesis and the complete restoration of the thymus involved the synchronous development of both the stromal and lymphocytic components.