The single occlusion technique (SOT) is a simple and noninvasive technique for measurement of passive respiratory mechanics in infants. Reference values based on measurements of a large population of healthy infants performed outside specialized research laboratories are lacking. The aim of this study was to present reference values for passive respiratory mechanics based on a large population of healthy term neonates and infants measured during natural sleep in routine care. As part of the ongoing Wheezing Illnesses Study Leidsche Rijn (WHISTLER), the compliance (C(rs)) and resistance (R(rs)) of the respiratory system were measured in 450 healthy unsedated neonates and infants with a mean age of 4.6 +/- 1.3 weeks. Multivariable regression analysis, with gestational age, age at measurement, body size, sex, and ethnicity as possible predictors, was carried out to estimate prediction equations for mean C(rs) and R(rs) values. Technically acceptable lung function measurements could be performed in 328 (73%) neonates and infants. Median C(rs) was 39.5 (range 14.8-79.1) ml/kPa and median R(rs) was 7.4 (range 3.8-19.5) kPa/L/sec. The following regression equations for C(rs) and R(rs) were obtained: ln C(rs) = 1.677 + 1.3 x 10(-4) x birth weight (g) + 0.030 x birth length (cm) and ln R(rs) = 2.496-3.1 x 10(-6) x birth length(3) (cm(3)) - 0.114 x sex. We provided reference values for passive respiratory mechanics using the SOT in a large population of healthy term neonates and infants measured during natural sleep. These data provide a frame of reference for assessing the normality of SOT measurements performed in routine care.