In a multicenter, double-blind, placebo-controlled trial that enrolled 215 premature infants with birth weights of 500 to 699 gm, 106 infants were treated prophylactically with a single 5 ml/kg dose of synthetic surfactant and 109 infants were given an equivalent dose of air placebo shortly after birth. In each group, 40 children survived infancy: 36 children in the air placebo group and 30 children in the synthetic surfactant group were available for follow-up. Weight, height, and head circumference measurements were similar for both groups at 1-year adjusted age. Infants who received synthetic surfactant at birth had statistically similar Bayley Scales of Infant Development scores (mental developmental index, 92 vs 83; psychomotor developmental index, 87 vs 82) compared with controls. Mild to moderate impairments in the synthetic surfactant group were 7% versus 29% in the control group; these differences were not statistically significant. The incidence of retinopathy of prematurity, the number of hospital readmissions, the need for surgery after day 28, evidence of chronic lung disease, the need for respiratory support at 1-year adjusted age, and the incidence of allergies were also not different between the two groups. However, the proportion of infants surviving without impairment was modestly higher in the synthetic surfactant group (8%, air placebo group; 23%, synthetic surfactant group). The findings from this small study indicate that infants weighing 500 to 699 gm who receive a single prophylactic dose of synthetic surfactant at birth have neurodevelopmental outcomes at least equivalent to those of infants given air placebo at 1-year follow-up.