IL-7 is produced by stromal cells and is the major lympho- and thymopoietic cytokine. IL-7 induces proliferation and differentiation of immature thymocytes, and protects thymocytes from apoptosis by induction of bcl-2 expression. The regulation of IL-7 production is poorly characterized, although down-regulation by transforming growth factor-beta (TGF-beta) has been described. We measured the serum levels of IL-7 before and after bone marrow transplant (BMT) in 32 children undergoing BMT for genetic diseases (severe combined immune deficiency (SCID) and thalassemia), aplastic anemia, and acute lymphoblastic and non-lymphoblastic leukemia (ALL and ANLL). Prior to BMT, the highest IL-7 levels were observed in patients with SCID and ALL, i.e. those patients with genetic or acquired lymphopenia. Patients with thalassemia and ANLL had normal levels of IL-7. Over the 8 weeks following BMT, the IL-7 levels of patients with SCID and ALL fell as the absolute lymphocyte count (ALC) increased. No detectable change in IL-7 levels was observed in the patients with thalassemia and ANLL. Levels of IL-7 were highest in the young infants with SCID compared to the age-matched controls. Together, the data demonstrate that serum levels of IL-7 in lymphopenic patients are inversely related to patient age and the absolute lymphocyte count (ALC). The inverse relationship to ALC suggests that there is either direct regulation of stromal production or more likely, binding of secreted IL-7 to lymphocytes expressing IL-7 receptors.