Because of current interest in use of a combination of glucocorticoid and thyroid hormones for prevention of respiratory distress syndrome we examined the effects of dexamethasone and triiodothyronine (T3), alone and in combination, on glycogen content and rates of fatty acid and phosphatidylcholine synthesis in fetal rat lung. The hormones were administered to the mothers on the 2 days before delivery on days 17-22 of gestation. Both hormones increased the rate of choline incorporation into phosphatidylcholine, an index of surfactant synthesis, on day 20 just prior to the normal developmental surge but had no effect on this parameter on days 19, 21, or 22. There is a developmental increase in lung glycogen on days 17-20 with a decrease thereafter and a developmental increase in the rate of fatty acid synthesis between days 20 and 21. The increases in glycogen content and fatty acid synthesis were accelerated by dexamethasone and prevented by T3and when the hormones were administered together T3antagonized the stimulatory effects of dexamethasone on these parameters. Both dexamethasone and T3accelerated the normal developmental decrease in lung glycogen later in gestation and the effects of the two hormones on this parameter were additive. The combination of dexamethasone and T3led to significantly smaller fetuses and increased mortality late in gestation. These data show that glucocorticoid and thyroid hormones have opposite as well as common effects on parameters of fetal lung maturation. Although the relationship between changes in lung glycogen or fatty acid synthesis and surfactant production are not known the combination of hormones may be beneficial at certain gestational ages but harmful at others. (Pediatr Res 20: 545-550,1986)