Fetal tracheal obstruction (TO) induces massive lung growth that could reverse or prevent the lung hypoplasia associated with experimental congenital diaphragmatic hernia. In the last three years, we have successfully developed a reversible technique of TO in the fetal sheep using balloon occlusion and have shown that 1 to 3 weeks of TO induces significant lung growth. However, the mechanism by which TO causes increased lung growth is still largely unknown. Presumably, the increased fetal airway pressure leads to increased pulmonary stretch, which causes increased cell proliferation, and this process in turn is likely mediated by specific peptide growth factors. In this study, the expression of insulin growth factor I and II genes (IGF-I, IGF-II) and the IGF receptor 1 gene (IGFr-1) was compared in fetal sheep lungs between animals with TO, TO with release of the occlusion before birth and untouched twin controls. The mRNA was assayed by Northern Blot on lung homogenate extract and normalized for the 18S ribosomal band. After 1 week of TO, IGF-I mRNA was increased 260% compared to controls (p <0.05). Changes in IGF-II mRNA (180% increase) and in IGF4-1 mRNA (170% increase) were less important but statistically significant. When the occlusion was released for 2 or 7 days, the expression of both IGF-I, IFG-II, and IGFr-1 mNRAs were comparable to controls. Preliminary in situ hybridization showed expression of IGF-I mRNA around large and medium artery in the lungs of animals with TO. The increase in IGF-II mRNA was comparable to a previous report (Hooper SB, Am J Physiol, 265:L403-409) showing a 177% increase after 1 week of TO. In the present study, however, we have demonstrated a temporal relationship between the increase expression of IGF mRNAs and the TO, and showed that the increase is not restricted to IGF-II. We speculate that the rapid lung growth associated with TO is mediated, at least partially, by the alteration in IGF-I, -II and IGFr-1 gene expressions. Support by Thelethon de la Recherche sur les maladies infantiles, and Fonds de recherche en Sante du Quebec.