We have utilized Serial Analysis of Gene Expression (SAGE) to analyze the temporal response of human pulmonary artery endothelial cells (HPAECs) to short-term chronic hypoxia at the level of transcription. Primary cultures of HPAECs were exposed to 1% O₂ hypoxia for 8 and 24 hours and compared to identical same passage cells cultured under standard (5% CO₂ 95% air) conditions. Hierarchical clustering of significant hypoxia-responsive genes identified temporal changes in the expressions of a number of well-described gene families including those encoding proteins involved in thrombosis, stress response, apoptosis, angiogenesis and cell proliferation. These experiments build upon previously published data describing the transcriptomic response of human aortic endothelial cells (HAECs) obtained from the same donor and cultured under identical conditions and we have thus taken advantage of the immortality of SAGE data to make direct comparisons between these two data sets. This approach revealed comprehensive information relating to the similarities and differences at the level of mRNA expression between HAECs and HPAECs. For example, we found marked differences in the cell type-specific response to hypoxia amongst genes encoding cytoskeletal factors, including paxillin, and proteins involved in metabolic energy production and the response to oxidative stress. These efforts contribute to the expanding collection of publicly available SAGE data and provide a foundation upon which to base further efforts to understand the characteristics of the vascular response to hypoxia in the pulmonary circulation relative to systemic vasculature.