OBJECTIVE To compare pulse oximetry oxygen saturation (SpO(2)) measured by a novel reflectance method from core body to arterial oxygen saturation (SaO(2)) in neonates and infants. Transmission pulse oximetry (TPO) was measured for comparison. METHODS We monitored 18 infants by the two pulse oximeters simultaneously. The reflectance pulse oximetry (RPO) (PRO2, ConMed, Utica, NY) was measured on the upper back or chest, while the TPO (N395-Nellcor, Pleasanton, CA) was measured from the finger of the infant on the left hand or feet. Data from the two methods were compared to functional SaO(2) derived from blood sample drawn from arterial line for patient care and measured by a Co-oximeter (Ilex, Instrument Lab. Lexington, MA). The potential advantage of the RPO is demonstrated in a case of a premature infant with hypovolemic shock, where SaO(2) or TPO could not be obtained but oximetry was available from the RPO. RESULTS We used for analysis 56 RPO and 32 TPO measurements. SpO(2) obtained from the RPO was 88.3+/-9.8%, from the TPO 84.2+/-10.1%, and functional SaO(2) was 88.2+/-11.7%, with correlation coefficient of 0.93 and 0.88, respectively (p<0.0001). The mean difference (bias) and standard deviation of the differences (precision) between the RPO and the TPO compared to functional SaO(2) were -0.09+/-4.5% and 1.26+/-5.9% and the absolute errors were 3.2+/-3.1%, and 4.4+/-4.0%, respectively. The accuracy of both RPO and TPO was diminished when SaO(2) was <85%, but only the RPO remained correlated with the functional SaO(2). CONCLUSIONS Reflectance pulse oximetry measured from core body of neonates and infants is accurate and reliable and is comparable to the transmission SpO(2) when compared to functional SaO(2). We speculate that the reflectance method might be advantageous in cases of poor peripheral perfusion in neonates and infants.