Cerebral hemoglobin concentration (cHbc), a major determinant of oxygen transport capacity in the brain, shows a considerable variability due to physiological and methodological factors. In order to determine the (relative) contribution of these factors, the cHbc variability within the first 6 hours of life was studied in 28 very preterm infants using near infrared spectrophotometry (NIRS). Mean cHbc values were 46.4 +/- 14.1 micromol/l (2.75 +/- 0.84 ml/100 g). Is the variability in cHbc related to the methodology of cHbc measurements or to physiological variables? A statistical model of stepwise regression (backward selection) with 13 independent variables and with cHbc as a dependent variable showed that, from the total variability of +/- 14.1 micromol/l, only 3.7 micromol/l (26%) were of methodological origin, while the major portion, 9.3 micromol/l (66%) were related to four physiological variables: birth weight, gestational age, blood glucose and transcutaneous carbon dioxide tension. The remaining 1.1 micromol/l (7.8%) were unexplained. We conclude that NIRS, which allows continuous monitoring of cerebral oxygenation and metabolism even in the first hours of postnatal life, is a valid technique to measure cHbc in very preterm infants. The major portion of the large variability of early cHbc registrations can be attributed to physiological factors.