We studied the effects of interleukin-1 (IL-1) and tumor necrosis factor (TNF) on mouse megakaryocytopoiesis to evaluate the role of these cytokines in reactive thrombocytosis associated with inflammation. Injections of IL·l or TNF to mice induced a significant increase in the megakaryocyte progenitor cell (CFU-Meg) count in the spleen. When IL·l and TNF were injected simultaneously, the splenic CFU-Meg count was remarkably increased compared with mice injected with either IL·l (p < 0.003) or TNF (p < 0.001) alone. On the other hand, neither IL·l nor TNF showed any megakaryocyte-potentiating or -stimulating effects in vitro. In the sera obtained 4 h after administration of IL·l, TNF or both, high megakaryocyte potentiating activities were found. Furthermore, an extremely high level of IL·6 was detected in the serum after administration of both IL·l and TNF. These results strongly suggest that IL·l and TNF stimulate megakaryocytopoiesis indirectly via other cytokine(s) induced from accessory cells, and that increased levels of IL·l and TNF play important roles in the development of reactive thrombocytosis caused by inflammation.