The effects of early vs late correction of acidosis on the clinical course of the respiratory distress syndrome (RDS) was evaluated in 82 pre-term infants weighing less than 2,250 grams. Criterion for inclusion into the study was a pH of less than 7.25 either from fetal scalp, cord or umbilical arterial blood samples within 20 min of age. The infants were randomly grouped into: A, birth weight <1500 gm, early treatment (intravascular NaHCO3 infusion within 30 min of age); B, <1500 gm, late Rx (2–3 hrs of age); C, 1501–2250 gms, early Rx, and D, 1501–2250 gm, late Rx, Infants were otherwise similarly managed. AT designated intervals predetermined clinical parameters were used to make the diagnosis and to grade the severity of RDS. No significant differences were observed in arterial blood pH and PO2 values between groups during the first 30 min of life prior to Rd. In the early Rx groups, the arterial blood pH was significantly higher during the first 12 hrs. Base deficits were significantly smaller for the first 3 hrs in the Group A and for the first 24 hrs for group C. The PaO2 and PaCO2 values were not significantly different between early and late Rx groups. The incidence of RDS between groups was similar. The degree of severity of RDS was significantly greater in the late treatment groups from 12–96 hrs of age. A higher mortality rate was observed in infants weighing between 1001–2250 gms with late Rx. This study suggests that early correction of neonatal acidemia favorably influences the course of RDS, and that it may reduce the mortality of infants between 1001 and 2250 gms.