Recently many findings indicate that GM-CSF plays an important role in the pathogenesis of acute and chronic lung diseases. In the present paper the production of this cytokine in human pulmonary microvascular endothelial cells (HPMEC) is investigated. In an in vitro study quiescent HPMEC did not express GM-CSF, either at the transcriptional or at the protein level. After activation for 4 hours with TNF-(30/300 U/ml), LPS (0.1/1 µg/ml) or IL-1ß (100 U/ml) a significant release of GM-CSF was measured by ELISA, with a time-dependent increase over 72h. IL-8 (4 ng/ml, 16 ng/ml, 64 ng/ml) or IL-1ß at a concentration of 10 U/ml did not induce the release of GM-CSF. HUVEC and the angiosarcoma cell line HAEND served as reference cell lines. GM-CSF release in HPMEC was significantly (p<0.025-0.05) less inducible by IL-1ß than in HUVEC. A constitutive expression of GM-CSF by HAEND was observed. Additionally, GM-CSF expression in vivo by the lung microvasculature was confirmed by immunohistochemistry in lung tissue. To our knowledge this is the first report of the ability of human pulmonary endothelial cells to synthesize and release GM-CSF. These results support the hypothesis that the lung microvasculature via the production of GM-CSF is a potential contributor to the cytokine network in lung diseases. This could be of particular importance in the pathogenesis of the acute respiratory distress syndrome (ARDS) in which endothelial dysfunction plays a central pathogenetic role.