To study the possibility that changes in fetal surfactant composition depend on the availability of inositol, we isolated surfactant material from lungs of fetal and neonatal rats and estimated their plasma inositol concentration. During the 18- to 22-day gestational period the amount of surfactant increases from 0.17 to 3.10 µmol phospholipids/g wet lung. From day 20 onward, 70% or more of the phospholipids is phosphatidylcholine. In this period the relatively high percentage of phosphatidylinositol (8%) in the lung surfactant decreases to 4% whereas the percentage of phosphatidylglycerol increases from 2 to 8% at parturition. During gestation the phospholipid/protein ratio of the surfactant material increase from 3 to 11 and the highest ratio is found immediately after birth. It decreases again 24 h after birth to values characteristic for surfactant from adult rats. The plasma inositol concentration drops during the 18- to 22-day period from 0.81 to 0.26 mmol/liter and a similar decrease in inositol concentration occurs in amniotic fluids. The phosphatidylglyercol/phosphatidylinositol ratio of surfactant correlated negatively with the fetal plasma inositol concentration. It is most likely that the reduction in the level of fetal plasma inositol resulting from a declining production and an increasing metabolism, causes the decrease in phosphatidylinositol and increase in PG content of the surfactant of the fetal rat.