Experimental aplastic anemia (EAA) can be induced in CBA/J mice when they are sublethally irradiated and injected with lymph node cells (LNC) from C3H/He mice. Mice injected with LNC die of severe pancytopenia and marrow aplasia. In the present study, cells from other anatomical locations and subsets of LNC were examined for their ability to induce and to modulate EAA. Of peritoneal, splenic, and thymic cells, only cells from the thymus had EAA activity. C3H/He bone marrow cells did not induce any adverse effects in sublethally or lethally irradiated CBA/J mice. LNC, when depleted of B or phagocytic cells, retained EAA activity. In contrast, LNC depleted of T cells had significantly less EAA activity. Furthermore, when T cells of LNC were separated into peanut agglutinin (PNA)-receptor-positive and negative fractions, only the PNA- cells were able to induce EAA. EAA activity was lost when LNC were irradiated (1000 rad). The inability of splenic or bone marrow cells to induce EAA could have been due to the presence of cells that suppressed EAA activity. When splenic or bone marrow cells were coinjected with LNC, EAA was not induced. Coinjected irradiated splenic cells, but not bone marrow cells, were still able to inhibit EAA activity. Bone marrow cells seemed to inhibit EAA by replacing stem cells that were lost during the EAA process. On the other hand, splenic cells appeared to suppress EAA activity of LNC. Thus, radiosensitive PNA- T cells of lymph nodes or thymus were capable of inducing EAA, and their activity could be modulated by radioresistant splenic cells.