The combination of chloral hydrate and nitrous oxide (N2O) is often used for sedation in pediatric dentistry. The purpose of this study was to determine the extent to which N2O increases the level of sedation and respiratory depression in children sedated with chloral hydrate. Thirty-two children, 1-9 yr, received chloral hydrate, 70 mg/kg (maximum 1.5 g), and then received N2O (30% and 50%). Hypoventilation (maximal PETCO2 > 45 mm Hg) occurred in 23 (77%) children during administration of chloral hydrate alone, in 29 (94%) breathing 30% N2O (P = 0.08 versus control), and in 29 (97%) breathing 50% N2O (P = 0.05 versus control). Mean PETCO2 was increased during 30% (P = 0.007) and 50% (P = 0.02) N2O administration. Using chloral hydrate alone, 8 (25%) children were not sedated, 10 (31%) were consciously sedated, and 14 (44%) were deeply sedated. Using 30% N2O, 2 children (6%) were not sedated, 0 were consciously sedated, and 29 (94%) were deeply sedated (P < 0.0001). Using 50% N2O, 1 child (3%) was not sedated, 0 were consciously sedated, 27 (94%) were deeply sedated, and 1 (3%) had no response to a painful stimulus (P < 0.0001). We conclude that the addition of 30% or 50% N2O to chloral hydrate often causes decreases in ventilation and usually results in deep, not conscious, sedation in children. CONCLUSIONS Pediatric sedation in the dental office often consists of nitrous oxide (N2O) after chloral hydrate premedication. We found that the addition of 30% or 50% N2O to chloral hydrate often causes decreases in ventilation and usually results in deep, not conscious, sedation in children.