The lung surfactant system matures faster in females than in males in late gestation. We sought to determine whether hyperoxia in newborn rats influenced effects of maturation and sex on surfactant protein (SP) mRNA accumulation. Methods: newborn rat pups (8 litters) were exposed to air or 95% oxygen(O2) for 1, 4, and 8 days (d), anesthetized, sexed, had lungs removed and frozen. Total lung RNA was extracted and analyzed by Northem blots probed with 32P labeled SP-A, B, and C cDNA. Results: SP-A mRNA: signal increased in air and O2 treated pups with age, but air exposed females showed greater abundance than males at 8 d, while O2 exposed males and females showed similar, but lower levels. SP-B mRNA: signal increased from 1 d to 4 d in air exposed females, and by 8 d declined to 1 d levels. With O2 the rise was absent at 4 d. In males, age had no effect on signal, but O2 led to a decline by 8 d. SP-C mRNA: in contrast to SP-A and B, signal in air treated males decreased at 4 d but by 8 d exceeded levels at 1 d. O2 eliminated the 8 d increase. Air treated female signal at 1 d exceeded male, but declined at 4 and 8 d. O2 had no effect. Effects of maturation, sex, and O2 exposure were noncoordinate among the surfactant protein mRNAs. In general the female pups showed greater surfactant protein mRNA accumulation than males at 1 d and with age, but this was reduced by treatment with O2. Effects of O2 on SP mRNA in male pups were less marked. The suppressive effects of O2 on the maturational increases in surfactant protein mRNAs may have unexpected adverse effects on lung function in newborns, particularly females.