ExtractTo test the hypothesis that fetal lung maturation can be accelerated by one of the xanthine derivatives, aminophyllin was given to 40 pregnant rabbits beginning on the 20th gestational day for a period of 7‐10 days. The fetuses were delivered by cesarean section and fetal lung maturity was assessed by determining the biochemical, functional, and ultrastructural characteristics of aminophyllin‐treatedvs.control animals. The phospholipid content of the lung tissue homogenate from the aminophyllin‐treated group was significantly higher than in the control subjects (saline injected) at 28 days of gestation (421 ± 9vs.368 ± 12 &mgr;g/mg wet wt, mean ± SEM) and at 29 days of gestation (531 ± 10vs.475 ± 20). The alveolar wash phospholipid content of the aminophyllin‐treated group was higher at 30 days (167 ± 9 &mgr;g/mg dry wt, mean ± SEMvs.117 ± 17). The lung compliance derived from pressure volume curves was also significantly higher in the aminophyllin‐treated group when compared with controls at 27 days of gestation (0.023 ± 0.0005 ml/cm H2O, mean ± SEMvs0.010 ± 0.0002) and at 28 days of gestation (0.048 ± 0.0003vs0.035 ± 0.0006). There was no significant difference in the number of lamellar bodies in the type II cells between the aminophyllin‐treated and the control groups. The data show that aminophyllin has accelerating effects on fetal lung maturation in rabbits when the drug is given to pregnant rabbits during the last 7‐10 days of gestation.SpeculationOur data do not permit extrapolation into the clinical application of utilizing xanthine derivatives for the enhancement of fetal lung maturation. However, they provide evidence that there may be several pharmacologic agents that might enhance fetal lung maturation by various mechanisms. These data may also provide impetus for some centers to review the statistical correlation of respiratory distress syndrome in infants born to mothers who have received xanthine derivatives during the latter part of pregnancy for the treatment of such conditions as bronchial asthma. If the latter clinical evidence is a positive one, it may be justified to initiate a clinical trial to evaluate the effect of xanthine derivative treatment of the mother for the purpose of preventing respiratory distress syndrome in the newborn infant.