Prenatal starvation causes pulmonary hypoplasia, retarded alveolarization, and reduced surfactant production in newborn guinea pigs. This study examined the potential benefit of simultaneous transplacental dexamethasone, which accelerates fetal lung maturation in other species. Pregnant guinea pigs were placed in 1 of 4 groups: Control (C), fed ad libitum until term (67 days) and given daily saline injections from Day 55 of gestation until term; Dexamethasone (D), fed as Group C but given daily injections of 2.0 mg dexamethasone/kg BW from Day 55 until term; Starved (S), given 50% rations from Day 45 until term and injected as Group C; Starved + Dexamethasone (SD), fed as Group S and injected as Group D. Controls and Group D did not differ in body or lung weight, DNA, protein, or lung volume (VL), but Group D lungs contained more lavageable and tissue surfactant, total alveolar surface area (Sa), and membrane diffusing capacity (DmO2) because of increased alveolar surface density. The S neonates weighed 38% less than controls, with proportional reductions in lung weight, DNA, protein, lavage and tissue phospholipids, VL, Sa septal tissue, capillary surface area (Sc), and DmO2. Compared with these S neonates, the SD neonates did not differ for BW, lung weight, DNA, protein, phospholipids, or VL, but their lungs contained significantly more Sa, Sc, epithelial and endothelial tissue volumes, and a higher alveolar surface density. These differences resulted in an average DmO2 for SD neonates that was indistinguishable from that of controls, and correlated with greater viability among the smallest SD animals compared with those in Group S.(ABSTRACT TRUNCATED AT 250 WORDS)