The proposed studies have been designed to investigate the development of pain response in the human infant. Clinical procedures routinely experienced by newborns in hospital nurseries will be utilized to study infant pain. The 187 subjects will include a range of premature and full term infants, with and without brain injury. Each infant will be studied during both manipulative, non-painful handling procedure and an invasive heel stick procedure. Infants will be studies shortly after admission and shortly before discharge from the nursery. Those requiring prolonged hospitalizations will be studied at weekly intervals until they are discharged or reach 40 weeks conceptional age. Because infant pain cannot be detected using traditional means of verbal report, alternative measures of behavioral state, cry and heart rate patterns, with an emphasis on vagal tone, will be utilized. The goals of the research are 1) to determine whether infants respond differentially to pain and non-pain stimuli; 2) to trace the development whether of infants' pain responses as a function of their prenatal and postnatal development; 3) to examine prenatal and perinatal factors that may influence the infants' responses to painful events; 4) to determine whether infants exhibit individualized, stable responses to pain over time; and 5) to determine whether early responses patterns to pain predict subsequent morbidity or behavior responsivity. The long-term goals of the proposed studies are to trace the development of the complex phenomena of pain in the human, to provide the data necessary to develop effective, clinical, pain-intervention strategies for newborns and infants, and to gain a better understanding of how the newborn infant responds to pain.