To examine the effect of epidermal growth factor (EGF) on lung parenchymal maturation in fetal rhesus monkey, recombinant human EGF was administered intraperitoneally (IP) at 66 mg/kg body wt over a 7-day period into the fetal peritoneal cavity alone or IP and into the amniotic fluid (AF) simultaneously. The saline carrier was injected IP and AF into control (CO) fetuses. The body weights of the IP + AF group were significantly larger than CO. Overall lung growth, measured as wet lung weight or fixed volume of the right cranial lobe, was unchanged. Fixed lung volume per gram body weight was significantly lower for both IP + AF and IP compared with CO. Morphogenesis of lung parenchyma, measured as percent parenchymal airspace or airspace size, was unchanged. Alveolar type II cell ultrastructure was significantly altered by EGF treatment; volume fraction of cytoplasmic glycogen was 50% less and lamellar bodies threefold greater for IP + AF and IP groups compared with CO. Total phospholipid content of AF was not altered, but relative percentages of different phospholipids were changed by EGF treatments; phosphatidylinositol was significantly reduced, and phosphatidylglycerol was significantly elevated. The lecithin-to-sphingomyelin ratio was unchanged. Surfactant apoprotein A concentration in AF was significantly elevated and was detected by immunoperoxidase in more cuboidal alveolar cells in EGF-treated animals when compared with CO. We conclude that exogenous EGF administered in the last trimester of pregnancy accelerates structural and functional cytodifferentiation of the alveolar type II cell in fetal primates. These maturational changes occur in the absence of significant alterations in overall lung growth or morphogenesis of the gas exchange area.