The mechanisms by which interleukin-1 (IL-1) stimulates hematopoiesis are not clear. We have previously shown that in vivo administration of IL-1 indirectly increases IL-1 receptor (IL-1R) expression on both immature and mature bone marrow (BM) cells, partly due to IL-1-induced hematopoietic growth factor (HGF) production. Because IL-1 also stimulates the hypothalamic pituitary-adrenal axis resulting in the production of glucocorticoids (GC), we assessed whether in vivo treatment with HGF and glucocorticoids upregulates IL-1R. Administration of IL-1 to adrenalectomized mice reduces by 53% IL-specific binding on light density bone marrow (LDBM) cells compared to sham-operated mice. The administration of dexamethasone (dex) alone induced only a slight increase in IL-1R expression but synergized with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), IL-3 and IL-6 to upregulate IL-1R expression. Flow cytometry analysis using the RB6-8C5 antibody, which is differentially expressed on myeloid cells, indicated that combined G-CSF and dex treatment acts to promote increased numbers of differentiated myeloid progenitors in the bone marrow. Autoradiographic analysis confirmed that while G-CSF and dex increased IL-1R expression on all myeloid cells, it was particularly pronounced for myelocytes, promyelocytes and metamyelocytes. These results suggest that the ability of IL-1 to enhance granulocyte differentiation in vivo is partly due to its ability to induce a cascade of cytokines and steroids which in turn regulate IL-1 receptor expression.