The effects of hematocrit and systolic blood pressure on cerebral blood flow were measured in 15 stable, low birth weight babies. CBF was measured with a modification of the xenon-133 (133Xe) clearance technique, which uses an intravenous bolus of 133Xe, an external chest detector to estimate arterial 133Xe concentration, eight external cranial detectors to measure cephalic 133Xe clearance curves, and a two-compartmental analysis of the cephalic 133Xe clearance curves to estimate CBF. There was a significant inverse correlation between hematocrit and CBF, presumably due to alterations in arterial oxygen content and blood viscosity. Newborn CBF varied independently of systolic blood pressure between 60 and 84 mm Hg, suggesting an intact cerebrovascular autoregulatory mechanism. These results indicate that at least two of the factors that affect newborn animal CBF are operational in human newborns and may have important clinical implications.