To evaluate the effect of body position on oxygenation and ventilation in neonates over a prolonged period, infants with respiratory disease were followed by transcutaneous (tc) monitoring for alterations in tcPO2 and tcPCO2 with position changes. In 14 studies of seven patients, prone positioning was compared with supine positioning over a 6-hour interval. All patients were premature, were receiving supplemental oxygen, and had respiratory disease secondary to prematurity. The median gestational age was 29 weeks; all infants were 2 months old or less at the time of the study. Prone positioning resulted in a significantly higher tcPO2; mean (+/- SD) tcPO2 increased from 63 (+/- 11.6) mm Hg to 71 (+/- 14.6) mm Hg, and decreased to 65 (+/- 11.2) mm Hg when the infant was returned to supine (P less than .05). This increase in tcPO2 was stable throughout 2 hours in the prone position. No significant change in tcPCO2 was detected. Infants were also found to spend a greater proportion of time sleeping when prone (75% +/- 13% vs 33% +/- 14%; P less than .05). These finding suggest that improvement in oxygenation with the prone position is stable over an extended period in the sick preterm infant.