While the spleen is an active site for myelopoiesis during the late embryonal and perinatal stages, the activity is gradually lost later. However, myelopoiesis in the adult spleen can be reactivated by irradiation or various stimulants. In this study we investigated factors which determine the myelopoiesis-supporting activity in the adult spleen. To address this question, we used scid mouse because virtually no lymphocytes, which might compete in the splenic microenvironment with hematopoietic progenitors, are present there. The results demonstrated: 1. Even in scid mouse, the myelopoiesis-supporting activity in the spleen is lost within a week after birth as in normal mice. 2. While myelopoiesis does not occur in the spleen of unstimulated scid mouse by bone marrow transfer alone, myelopoiesis in the spleen is reactivated by irradiation or lipopolysaccharide (LPS) application. 3. Myelopoiesis in the spleen induced by irradiation is dependent on c-kit and its ligand steel factor (SLF), because it was suppressed completely by the monoclonal antibody (mAb) against c-kit. 4. The expression of SLF transcripts in the spleen was enhanced after irradiation. These results suggest that the factor which determines myelopoietic activity in the spleen resides primarily in the status of the splenic microenvironment.