Estimations of cerebral blood flow were performed by both near infrared spectroscopy and 133xenon clearance on 12 occasions in nine critically ill premature infants (26-29 gestational wk) who required mechanical ventilation and supplemental oxygen. For each study, one determination of cerebral blood flow by 133xenon was compared with the mean of two to five measurements by near infrared done within 1-19 (median 5) h. 133Xenon measurements ranged from 9.6-16.9 mL/100 g/min, and mean near infrared measurements ranged from 8.6-25.0 mL/100 g/min. There was a significant correlation between the two sets of measurements (r = 0.80, p < 0.001). The mean difference between the methods was 1.6 mL/100 g/min, and the 95% limits of agreement were -0.5-3.8 mL/100 g/min. This study showed that cerebral blood flow can be measured noninvasively in critically ill premature infants at the cotside by near infrared spectroscopy and by the 133xenon clearance technique. The methods give comparable results.