Tumor necrosis factor (TNF)-alpha is a key pro-inflammatory cytokine, thought to be important in the pathogenesis of pulmonary emphysema. TNF-alpha overexpression in the lung leads to the phenotypic features of pulmonary emphysema, pulmonary hypertension, and right ventricular hypertrophy in mice bred in Denver, 5240 feet/1600 m of altitude. This study hypothesized that the altitude could affect the development of pulmonary emphysema as well as pulmonary hypertension. To investigate the effect of the altitude, TNF-alpha transgenic mice were bred at sea level, Fukuoka, Japan. The pulmonary physiology and histology demonstrated similar development of pulmonary emphysema, compared to the mice bred in Denver. With respect to pulmonary hypertension, right ventricular hypertrophy was attenuated. Interestingly, mortality rate was significant lower in the mice bred at sea level. In contrast with the results in Denver, a significant decrease of vascular endothelial growth factor (VEGF) and its receptors expression was not found. From these data, we consider that the altitude affects development of pulmonary hypertension through the expression of VEGF and its receptors. In contrast, the effect of altitude was not clear regarding the development of pulmonary emphysema.