Several recent studies show that production of platelets and red blood cells (RBC) are inversely related. For example, it is well established that hypoxia, a stimulator of erythropoiesis, causes thrombocytopenia in laboratory animals. The thrombocytopenia is most likely the result of a reduction in the production of platelets caused by a decrease in the number of colony-forming units-megakaryocyte (CFU-Meg), early precursor megakaryocytes (small acetylcholinesterase-positive cells, SAChE+), and recognizable megakaryocytes in the bone marrow. In all cases, active erythropoiesis was required for the thrombocytopenia. The hypoxia-induced thrombocytopenia was not caused by sequestration of platelets in an enlarged spleen or by expanding blood volumes. We speculate that this thrombocytopenia is caused by competition of a precursor cell of the erythrocytic and megakaryocytic cell lines; that is, marked stimulation of the erythroid cells by erythropoietin (Epo) causes a decrease in the number of immature megakaryocytes, leading to decreased thrombocytopoiesis. In support of this hypothesis, other recent work shows that thyroxine (a stimulator of erythropoiesis) and Epo (when given in large, chronic doses) elevate erythropoiesis and cause thrombocytopenia. Conversely, both endogenous and exogenous sources of thrombopoietin lead to elevated thrombocytopoiesis and anemia in mice. It should also be mentioned that megakaryocytes and erythrocytes have several biochemical similarities, and several clinical conditions point to an inverse relationship between RBC and platelet production. These in vivo, biochemical, and clinical data support the hypothesis that megakaryocytes and erythrocytes share a common precursor cell.