['To examine the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in thrombopoiesis.', 'Thrombopoietin-unresponsi ve mice (mpl null mice), which have a profound reduction in platelets and mature megakaryocytes, were interbred with mice that do not respond to GM-CSF or interleukin 5 (betac null mice), and hematopoiesis was examined. In initial experiments on a mixed genetic background, double mutant mice (betac/mpl null mice) showed an unexpected amelioration of the thrombocytopenia seen in mpl null mice. Platelet counts were elevated approximately twofold in betac/mpl null mice compared with mpl null mice (mpl null 73+/-31; betac/mpl null 164+/-70; n = 10 to 29 mice per genotype, p<0.00001). This was associated with lessening of the deficit of megakaryocytes, progenitor cells, and colony-forming units spleen seen in mpl null mice. This amelioration of the mpl null phenotype in betac/mpl null mice on a mixed genetic background was highly statistically significant. To determine whether this amelioration of phenotype was solely the consequence of loss of betac signaling, progeny of a second intercross on a C57BL/6 background (B6betac/mpl null mice) were examined. When the resulting B6betac/mpl null mice were analyzed and compared with B6mpl null littermates, the increase in platelet count, hematopoietic progenitor cell number, and colony-forming units spleen number was no longer observed.'] Is granulocyte-macrophage colony-stimulating factor responsible for residual thrombopoiesis in mpl null mice?