A noninvasive optical method for bedside monitoring of cerebral oxygenation in small preterm infants was evaluated. Through differential absorbance of near infrared light, changes in the oxidation-reduction level of cytochrome aa3, in the oxygenation state of hemoglobin and in tissue blood volume were assessed in the transilluminated anterior cerebral field. Overall, cerebral oxygenated hemoglobin correlated significantly with transcutaneous oxygen, r = .44 p less than .0001; however, correlation was best in the absence of cardiorespiratory disease. Hypoxia with or without bradycardia led to hemoglobin deoxygenation and a shift in cytochrome aa3 to a more reduced state. When hypoxic episodes came in series or were prolonged, aa3 reduction occurred simultaneous with hemoglobin deoxygenation but its recovery to base-line values sometimes lagged behind the return of hemoglobin oxygenation. In one infant with a large patent ductus arteriosus, even brief episodes of mild bradycardia caused precipitous reduction of cytochrome aa3 before any shift to greater hemoglobin deoxygenation. This response disappeared after ductal ligation. In general, the antecedent state of cerebral oxygenation, the severity and duration of deoxygenation, and the presence or absence of circulatory abnormalities all influenced the aa3 response to hypoxia. Continuous noninvasive near infrared monitoring of cerebral oxygenation can be performed on sick preterm infants at the bedside.