The ability of epidermal growth factor (EGF) to induce lung maturation was evaluated in fetal and neonatal lambs. EGF was infused (3-5 days) into one member of 10 fetal twin pairs, one member of 2 term twin pairs, and 2 singleton term lambs. All EGF-treated lambs had evidence of epithelial hyperplasia of the conducting airways typical of the EGF effect. With the exception of the most immature pair, the lungs of treated versus control lambs were judged more mature by morphologic criteria by use of light and electron microscopy. None of the 6 premature lambs treated with EGF and allowed to breath showed evidence of hyaline membrane disease, while 3 untreated control lambs developed typical hyaline membranes when delivered by cesarean section after maternal hypotension. All untreated control animals showed more severe clinical symptoms of respiratory distress than did the EGF-treated animals.