This article reviews experience with longitudinal follow-up of high-risk infants in the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network. In 1993, the Network initiated a research protocol to provide longitudinal follow-up of infants with birth weight less than 1001 g and infants with higher birth weights who participated in certain Network randomized trials. Infants are assessed at 18 to 22 months corrected age (corrected for degree of prematurity) using measures of the infant's health, growth, neuromotor, and early cognitive functioning, language, behavior, and family resources. Data from these assessments have been used to investigate potentially modifiable risk factors for cerebral palsy and delayed early cognitive functioning and to evaluate the risks and benefits of interventions assessed in randomized trials. The Network's experience thus far suggests that longitudinal follow-up can provide valuable information about treatments given to fetuses and neonates.