We have previously demonstrated that ovariectomy causes an increase in the number of colony-forming unit granulocyte/macrophage (CFU-GM) and an upregulation of osteoclastogenesis in mice, both of which are mediated by interleukin-6 (IL-6). IL-6 is involved in the development of several hematopoietic progenitors, including the burst-forming unit-erythroid (BFU-E) and multipotent CFUs (CFU-GEMM). Therefore, we performed studies to examine if other hematopoietic progenitors, besides CFU-GM and their progeny, are affected by estrogen loss. We found that ovariectomy caused an increase in the number of CFU-GEMM and BFU-E, as well as an increase of CFU-GM in marrow cells of the femur. Administration of 17 beta-estradiol or a neutralizing antibody against IL-6 prevented the ovariectomy-induced increase in the number of these progenitors in the marrow. Ovariectomy also caused an increase in the number of circulating lymphocytes, neutrophils, and monocytes, which were suppressed by administration of 17 beta-estradiol or the neutralizing antibody against IL-6; however, the number of circulating platelets was unaffected by loss of ovarian function. These data establish that, in addition to upregulation of osteoclastogenesis, loss of estrogens in the mouse causes widespread effects on hematopoiesis, which are apparently mediated by IL-6.