The ratio of pulmonary vascular resistance to systemic resistance was determined before and after oxygen administration in 25 children with an isolated large ventricular septal defect and elevated pulmonary vascular resistance (pulmonary/systemic resistance ratio, Rp/Rs greater than 0.25). A fall of 30% or more in the Rp/Rs, after 20 minutes of oxygen inhalation (FiO2 greater than 0.90), was considered a positive response to oxygen. In the 6 children with Down's syndrome, the Rp/Rs fell significantly more in oxygen (52%) than it did in the 19 children without Down's syndrome (31%, p less than 0.05). No other clinical or baseline hemodynamic finding was predictive of vascular responsiveness. Seventeen children underwent closure of the ventricular septal defect. Three of 11 children who responded to O2 expired shortly after operation; each of the 6 children who did not respond to O2 survived operation. Two of the deaths (occurring less than 12 hours after closure) were from low cardiac output; a third child died suddenly 5 days postoperatively. Thirteen children, 7 who responded to oxygen and 6 who did not, were restudied by cardiac catheterization an average of 2.0 years following successful closure of the ventricular septal defect. While the Rp/Rs in room air fell following closure of the defect in both groups, the decrease was 22% in responders and 28% in nonresponders. The results of this study, unlike similar studies performed at higher altitudes, suggest that the preoperative responsiveness of the pulmonary vasculature to oxygen does not predict either operative survival or postoperative pulmonary vascular resistance.