Vascular endothelial growth factor (VEGF) production was analysed in megakaryocytic cell lines and CD34(+) haematopoietic progenitors following treatment with thrombopoietin (TPO), In CMK cells TPO caused a time- and dose-dependent increase in the levels of VEGF released into the medium, A similar effect was observed in UT-7/mpl cells transfected with the TPO receptor c-Mpl, but not in parental UT-7 cells, In CD34(+) haematopoietic progenitor cell cultures TPO stimulated VEGF mRNA expression and VEGF protein release, Production of VEGF in CD34(+) cultures increased with TPO-induced megakaryocytic differentiation, but not with erythroid or myelomonocytic differentiation induced respectively by erythropoietin and granulocyte-macrophage colony-stimulating factor, These results demonstrate that TPO stimulates VEGF release in c-Mpl-expressing cells and suggest that this process is an integral feature of the megakaryocytic differentiation programme. (C) 1998 Federation of European Biochemical Societies.