Our purpose was to determine whether docosahexaenoic acid increased surfactant production, as reflected by increased dipalmitoyl phosphatidylcholine, in mouse fetal lung and amniotic fluid.On day 9.5 of gestation, pregnant mice were given docosahexaenoic acid orally at 0, 5, 10, or 20 mg per day and were killed at day 16.5 (preterm) and day 19.5 (term) of gestation. Dipalmitoyl phosphatidylcholine was measured in fetal lung homogenates and amniotic fluid by high-performance thin-layer chromatography.Dipalmitoyl phosphatidylcholine values in lung were 0.22 +/- 0.27 microg/mg of total protein in preterm versus 1.96 +/- 0.57 microg/mg in term control fetuses. Pretreatment with 5, 10, or 20 mg docosahexaenoic acid increased dipalmitoyl phosphatidylcholine levels in preterm fetuses to 1.20 +/- 0.75, 1.60 +/- 0.67, and 3.28 +/- 0.44 microg/mg of protein, respectively. A similar trend was observed in amniotic fluid in which dipalmitoyl phosphatidylcholine levels were 1.86 +/- 3.70 microg/mL in preterm fetuses at baseline and increased to 7.81 +/- 1.21, 16.83 +/- 1.62 and 22.72 +/- 3.44 microg/mL after pretreatment for 7 days with 5, 10, and 20 mg docosahexaenoic acid (P.05 compared to untreated mice). Dipalmitoyl phosphatidylcholine levels in amniotic fluid were 24.46 +/- 10.3 microg/mL in term control mice.The oral administration of docosahexaenoic acid to pregnant mice during pregnancy can induce dipalmitoyl phosphatidylcholine production and secretion, which is the major lipid component of surfactant.