Abstract At least two human preproendothelin-1 mRNAs are produced by a single gene through the use of different promoters, and the mechanisms controlling the production of these alternative transcripts might be cell-specific. In human lung, endothelin-1 is produced by vascular endothelial cells, bronchial epithelial cells, and pulmonary monocytes/macrophages. Given the important role of endothelin-1 in the pathogenesis of some pulmonary diseases, we carried out a functional analysis of the preproendothelin-1 gene promoter(s) in bronchial epithelial cells and lung monocytes. Two distinct preproendothelin-1 mRNAs were expressed in the two cell populations. Using deletion mutants and enhancer trap transfection experiments, we also identified different regions of the preproendothelin-1 gene necessary for endothelin-1 expression in bronchial epithelial cells and pulmonary monocytes.