To study their effects on tracheal fluid (TF) production and surfactant flux, we gave 12-h infusions of prostaglandin synthetase inhibitors (PGSI) on 16 occasions to 10 fetal lambs at gestational ages (GA) of 125--141 days. Results were similar with both sodium meclofenamate (13.9 +/- 3.4 mg.kg-1, 12 studies) and indomethacin (33.6 +/- 8.0 mg.kg-1, 4 studies). All studies were done at least 6 days after surgery and 4 days before spontaneous birth. During infusions of PGSI, there were no changes in fetal arterial blood pressure, pH, PaO2, PaCO2, TF production or its concentration of sodium, potassium, and chloride; calcium concentration in TF increased slightly. We expressed tracheal surfactant flux as micrograms.kg-1.h-1 of saturated phosphatidylcholine (SPC). If control SPC flux was less than 5 micrograms.kg-1.h-1 (10 studies at GA of 125--141 days), it did not change during infusion of PGSI; however, if control was greater than 5 micrograms.kg-1.h-1 (6 studies at GA 132--140 days), SPC flux decreased during the infusions in all studies. The results suggest that prostaglandins do not strongly influence TF production up to 4 days before birth and that prostaglandins are involved in the increased flux of surfactant which occurs in late gestation.