In vivo administration of recombinant human interleukin-1 beta (rHu IL-1 beta) selectively enhanced the recovery from granulocytopenia and thrombocytopenia caused by whole body irradiation, in a dose dependent manner. Since IL-1 itself in vitro had no colony-stimulating activity (CSA), we studied whether IL-1 can produce hematopoietic factors in vivo, which in turn will promote granulopoiesis and thrombopoiesis. Serum from IL-1 injected mice showed marked granulocyte/macrophage CSA (GM-CSA), but little megakaryocyte CSA (Meg-CSA). Interestingly, strong megakaryocyte potentiator (Meg-POT) activity was detected in the serum. Further analysis of the serum by gel filtration chromatography showed that Meg-POT activity could be eluted in different fractions from GM-CSA. Since erythropoietin which is known to stimulate erythropoiesis also exhibited remarkable Meg-POT activity, serum from IL-1 injected mice were assayed for erythroid CSA. We found that unlike erythropoietin the serum showed no erythroid CSA. Taken together, these results suggest that IL-1 may potentiate granulopoiesis and thrombopoiesis by producing at least two distinct types of hematopoietic growth factors in vivo, namely granulocyte/macrophage colony-stimulating factor and a thrombopoietin-like factor.