The development of microcephaly after significant hypoxic-ischemic cerebral injury in the full-term newborn has major prognostic significance. However, the onset of microcephaly in this context may be delayed more than 12 months. OBJECTIVES. To determine whether serial head circumference measurements and decreased rate of head growth in asphyxiated full-term newborns during the first few months of life may predict the development of eventual microcephaly. METHODOLOGY. Serial head circumference measurements at 4, 8, and 18 months of age were obtained in 54 full-term newborns who had acute, hypoxic-ischemic encephalopathy. The rate of head growth was determined on the basis of changes in head circumference ratios which are calculated as follows: actual head circumference/mean head circumference for age x 100%. Head circumference ratios were correlated with severity of newborn encephalopathy and outcome at 18 months. RESULTS. A decrease in head circumference ratios of > 3.1% between birth and 4 months of age was highly predictive of the eventual development of microcephaly before 18 months (sensitivity 90%, specificity 85%). CONCLUSIONS. These data demonstrate that serial head circumference measurements during the first 4 months of life and calculation of decreased rate of head growth in full-term newborns with hypoxic-ischemic encephalopathy may predict microcephaly before its actual occurrence.