We sought to determine the impact of HIV in pregnancy on rates of prematurity, low birth weight (LBW), and neonatal respiratory morbidity in the offspring of HIV positive mothers. From 1990 to 1994, 599 neonates born to HIV positive mothers (51% black, 12% white, 31% Hispanic, 6% others) were enrolled at five centers in the U.S. Of the 599, 92 were HIV positive, 454 were HIV negative, and 53 died or were lost to followup. Incidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), meconium aspiration syndrome (MAS), and neonatal pneumonia was compared to anticipated rates for HIV unexposed neonates of comparable gestation and birth weight. Rates of prematurity (<37 weeks), LBW (<2.5 kg), and VLBW (<1.5 kg) were 19, 17.7, and 3.3%, respectively in the infants of HIV positive mothers, greatly exceeding comparable rates for the U.S. population, corrected for race. The incidence of RDS was 3% (17/599) which coincided with the anticipated rate after adjusting for prematurity and birth weight. Of 16 infants <1.5 kg, 31% (5/16) developed BPD. Only 3/599 infants developed mild MAS and none had documented neonatal pneumonia. Lower gestational age (weeks) was associated with increased odds of HIV infection (p=0.01) in the infants after adjusting for race. We conclude that 1) infants born to HIV positive mothers exhibit very high prematurity and LBW rates; 2) the odds of prematurity are higher in infected (vs uninfected) infants; and 3) the incidence and severity of neonatal respiratory morbidity are no higher than available data from HIV unexposed neonates. We speculate that good prenatal and neonatal care can minimize respiratory morbidity in this high risk population.