The authors test the null hypothesis that maternal caffeine administration will not significantly alter fetal cerebral oxygenation. The authors measured fetal arterial blood gases, cortical tissue O(2) tension (tPO(2)), sagittal sinus blood gases, and laser Doppler cerebral blood flow in response to a 30-minute caffeine infusion (400 mg intravenously) into 7 near-term pregnant ewes, and they calculated fractional O(2) extraction and relative cerebral metabolic rate for O(2) (CMRO(2)). Following maternal caffeine infusion, both fetal cortical tPO(2) and sagittal sinus (HbO(2)) decreased significantly, from 10.7 +/- 0.9 to 6.8 +/- 1.1 Torr and from 46% +/- 2% to 37% +/- 6%, respectively. This was associated with significant 20% to 30% increases in fractional O(2) extraction and CMRO( 2). Fetal arterial blood gas values did not change significantly. In conclusion, maternal caffeine administration significantly decreases cerebral oxygenation without affecting systemic oxygenation in fetal sheep. The authors speculate that for a fetus that may be otherwise compromised, this increase in CMRO(2) with decreased cortical tPO(2) could present a problem.