Transforming growth factor (TGF)- is a family of multifunctional cytokines controlling cell growth, differentiation, and extracellular matrix deposition in the lung. The biological effects of TGF- are mediated by type I (TR-I) and II (TR-II) receptors. Our previous studies show that the expression of TR-II is highly regulated in a spatial and temporal fashion during lung development. In the present studies, we investigated the temporal-spatial pattern and cellular expression of TR-I during lung development. The expression level of TR-I mRNA in rat lung at different embryonic and postnatal stages was analyzed by Northern blotting. TR-I mRNA was expressed in fetal rat lungs in early development and then decreased as development proceeded. The localization of TR-I in fetal and postnatal rat lung tissues was investigated by using in situ hybridization performed with an antisense RNA probe. TR-I mRNA was present in the mesenchyme and epithelium of gestational day 14 rat lungs. An intense TR-I signal was observed in the epithelial lining of the developing bronchi. In gestational day 16 lungs, the expression of TR-I mRNA was increased in the mesenchymal tissue. The epithelium in both the distal and proximal bronchioles showed a similar level of TR-I expression. In postnatal lungs, TR-I mRNA was detected in parenchymal tissues and blood vessels. We further studied the expression of TR-I in cultured rat lung cells. TR-I was expressed by cultured rat lung fibroblasts, microvascular endothelial cells, and alveolar epithelial cells. These studies demonstrate a differential regulation and localization of TR-I that is different from that of TR-II during lung development. TR-I, TR-II, and TGF- isoforms exhibit distinct but overlapping patterns of expression during lung development. This implies a distinct role for TR-I in mediating TGF- signal transduction during lung development.