Little is known about the effects of hyperoxia on the cerebral circulation of human infants. Using duplex Doppler we measured the changes in cerebral blood flow velocity in a group of full term (n = 15) and premature infants (n = 17, median gestational age 31 weeks) in response to a transient threefold increase in oxygen tension. Measurements of blood gas tensions as well as blood pressure and cerebral blood flow velocity were made over a period of 20 minutes on three occasions for each infant; during normal oxygenation, hyperoxia, and normal oxygenation. There was a fall in cerebral blood flow velocity in 15 of the 17 premature infants with hyperoxia and the median reduction was 0.06 cm/second for every 1 kPa increase in oxygen tension. There was no significant change in either PCO2 or blood pressure during the period of hyperoxia. The cerebral blood flow velocity fell in all 15 infants born at full term during hyperoxia, but there was a simultaneous and significant reduction in PCO2 at the same time as the hyperoxia. Analysis of variance suggested that in the infants born at full term the change in carbon dioxide had most effect in the reduction of cerebral blood flow velocity, rather than the hyperoxia itself. We conclude that in premature infants, cerebral vascular resistance may be altered by a fall in cerebral blood flow velocity in the presence of hyperoxia.