In the final stages of lung development, endothelial cells (EC) proliferate and alveolar capillaries develop in close proximity to the alveolar epithelium. The factors that regulate these processes are not known. VEGF is a specific EC mitogen and angiogenic factor that also modulates EC permeability. flk-1 is a high affinity signal transducing receptor for VEGF. Because the VEGF/flk-1 system has a major role in angiogenesis, we hypothesized that VEGF and flk-1 mRNA expression increase in developing mouse lungs. We investigated VEGF and flk-1 expression in fetal (d13,d15,d18), postnatal (d2, d8, d14) and adult mouse lungs. Northern and slot blot hybridizations were performed using a highly homologous rabbit probe for VEGF and a mouse probe for flk-1. Signal was quantified by phosphorimaging and compared to the housekeeper riboprotein L-32. As expected, Northern hybridization of VEGF and flk-1 showed transcripts of approximately 3.5kb and 5.5kb, respectively. Expression of both VEGF and flk-1 mRNA increased 3 fold between d13 and d18 of fetal life. During the first two weeks of postnatal life, when alveolarization occurs, both messages increased 3 fold further, rising to values found in adult lung. In situ hybridization of adult lung showed VEGF mRNA expression mainly by cells in alveolar septae. We conclude that VEGF and flk-1 expression increase in parallel during lung development. We speculate that VEGF from alveolar cells may regulate alveolar EC proliferation and capillary permeability in developing and adult lung. Supported by SCOR HL36453 and the Strong Children's Research Center.