Pain in children has been historically undertreated for a variety of reasons, including the complexity of pain assessment, inadequate research and training, and assumptions concerning pain. Lack of consistency in pain assessment and personal attitudes about pain have been identified as concerns in the NICU population. Some of the factors that are thought to affect caregivers include personal experience with pain and the idea that some procedures are more painful than others. Nurses currently have insufficient assessment tools and limited education about pain assessment in non-verbal infants. Personal beliefs also vary widely as to the nature and intensity of pain. The problem is further compounded by the abstract nature and the possible range of responses to painful stimuli. Behavior is the main source of information in nonverbal infants. However, depletion of an infant's response capacity can occur rapidly with stress, gestational age, and illness. In addition, behavioral responses may also be affected by multiple interventions, intubation, and paralytic drugs. Specific facial and motor behaviors were observed responses to pain in this sample of infants as well as increased heart rate and oxygen desaturation. No one single behavior constitutes an unequivocal measure of infant pain. However, characteristic patterns of distress have emerged from analysis of infant facial expressions, motor responses, and cries. Frequent and prolonged pain may be potentially harmful to the developing nervous system and may threaten the physiologic stability of premature and sick term infants. Whether or not a premature infant has the capacity to perceive pain is not in question, but these infants do have limited abilities to express their pain. Defining common behaviors that consistently appear with painful stimuli will assist in the identification of pain so that appropriate interventions to assess and to relieve pain can be planned. A variety of factors complicates the observation of neonates in an NICU. Premature birth, range of physiologic stability, the level of activity in the environment, and other possible sources of discomfort may confuse or blunt observations. While this observational design was difficult, it succeeded in delineating behaviors associated with a painful stimulus that provides a basis for further study.