Objective: We examined the trend in mortality caused by respiratory distress syndrome (RDS) and its impact on changes in infant and neonatal mortality rates (IMR, NMR) in the United States. Study design: Data on infant deaths in the United States for the period 1970 through 1995 were used to compare RDS-specific IMR to other cause-specific IMR. Data from the U.S. birth cohorts of 1985 through 1991 were used to examine birth weight- and RDS-specific NMRs. Results: IMR from RDS declined from 2.6 per 1000 live births in 1970 to 0.4 per 1000 in 1995. More than three quarters of this decline occurred between 1970 and 1985. RDS-specific NMR declined by 13% between 1985 and 1988 and by more than twofold greater, that is, 28%, between 1988 and 1991. There was also a significant reduction in postneonatal mortality from chronic lung diseases between 1988 and 1991. Conclusions: Most of the reduction in mortality from RDS occurred before the introduction of surfactant therapy. The recent accelerated reduction in mortality from RDS between 1988 and 1991 was temporally associated with widespread use of surfactant therapy and was the single most important factor for reduction in overall NMR in the United States.(J Pediatr 1999;134:434-40)