We derived a noninvasive method to compare changes in cranial blood volume during mechanical ventilation with changes occurring during spontaneous breathing in newborn infants. In ten infants receiving mechanical ventilation, cranial blood volume increased during inspiration by a mean of 8.3%. We found a consistent relationship between clinical estimation of lung compliance and the amount of cranial volume expansion. During spontaneous breathing in ten infants cranial blood volume decreased during inspiration by a mean of 5.8%. The findings indicate the need for careful monitoring during periods of rapid changes in lung compliance.