Neutropenia, as defined by common reference values, occurs often in neonates. Its incidence, causes, and clinical consequences have not been studied extensively in premature neonates. Of 208 consecutive infants with birthweight up to 2000 g, 121 (58%) had neutropenia. Low gestational age and low birthweight correlated with the incidence of neutropenia. Less than half of the neutropenic episodes could be attributed to infections, the others were related to specific perinatal events and due to drug therapy or were of unknown cause. Neutropenia following treatment with certain antibiotics was the most common cause of neutropenia occurring after the second week of life. The high incidence of neutropenia in premature neonates raises questions about application of these reference ranges to low birthweight infants and suggests the need for new reference values.