The objective of this study was to investigate the relationship between intraventricular hemorrhage (IVH) and cystic periventricular leukomalacia (PVL) with changes in the peripheral blood count. Total peripheral leukocytes, absolute neutrophils, platelets, and nucleated erythrocytes from the first 3 days after birth were compared in very-low-birth-weight infants with (n = 100) and without (n = 388) IVH and cystic PVL (n = 16). After controlling for potential confounding variables, infants with IVH had an increase in total leukocytes and absolute neutrophils and a reduction in nucleated erythrocytes compared with infants without IVH. No difference in any parameters studied was evident with regard to cystic PVL. After controlling for potential confounding variables by logistic regression, infants with a peripheral leukocyte count greater than 25,000/mm(3) beyond 24 hours of age had an odds ratio of 2.1 (95% confidence interval = 1.1-4.3) for developing IVH. We conclude that IVH is associated with an increase in total leukocytes and absolute neutrophils for 72 hours after birth in very-low-birth-weight infants. Further investigation is required to determine whether this leukocytosis is important in the pathophysiology of brain injury or is an associated factor.