According to animal studies myoinositol decreases surfactant phosphatidylglycerol and increases phosphatidylinositol. In the present study lung effluent phospholipids and serum myoinositol were analyzed in respiratory distress syndrome (RDS, 19 cases), in other lung disease (6 cases) and in 22 newborn with no lung disease. In addition, myoinositol was studied in amniotic fluid and in serum from umbilical vessels and from maternal vein (15 healthy newborn). There was a significant correlation between the fetal and amniotic fluid levels of myoinositol, but no detectable correlation between fetal and maternal myoinositol. Serum myoinositol was higher in preterm than in term newborns. In healthy newborns there was a negative correlation between lung effluent phosphatidylglycerol (expressed as percent of the phospholipids) and serum myoinositol (r = -0.968), and a positive linear correlation between myoinositol and lung effluent phosphatidylinositol (r = 0.849). In RDS at birth, undetectable phosphatidylglycerol corresponded with high serum myoinositol. During the first 5 neonatal days serum myoinositol either (1) decreased and phosphatidylglycerol appeared, (2) remained high and phosphatidylglycerol correspondingly low in some small preterm infants, or (3) decreased but phosphatidylglycerol did not expectedly increase and disaturated lecithin/sphingomyelin ratio remained low in other small preterm babies. We propose that a premature decrease in serum myoinositol among small preterm infants with RDS is not beneficial, since myoinositol may promote hormone-induced lung maturation and healing of lung damage.