This paper describes a new, less toxic and more selective approach to study the adult thymus. An adriamycin (ADR), sparing bone marrow (BM) stem cells and nontoxic to cells that are not in cycle during treatment, was used as a depleting agent in conjunction with vascular thymus transplantation. We were able to deplete the thymus of thymocytes without damaging its microenvironment as witnessed by intact antigen profiles of stromal cells. Two models were used in this study, (1) regeneration after ADR induced depletion with or without BM reconstitution either systemically or intrathymically and (2) thymocyte turnover or regeneration in vascularly transplanted thymi. In the latter model either normal thymus was grafted into ADR treated recipient or ADR depleted thymus was grafted into normal recipient. These experiments clearly show that intact BM function is a prerequisite for intact continued cellularity of the adult thymus. Although the resident thymocyte population possesses some limited proliferating potential, it clearly does not seem to have a permanent self-renewing capacity of intrathymic stem cells.