OBJECTIVE: Previous reports have shown that pain is managed inadequately in newborn infants. Ironically, clinicians believe that infants can experience pain much like adults, that infants are exposed daily to painful procedures, and that pain protection should be provided. In adults, a close relationship has been shown in how adults behave in response to pain, how painful they sense the stimulus to be, and physical measurements of the intensity of the stimulus. Whether similar parallels exist in newborn infants has not been examined. If these parallels do not exist in infants, it may help explain why clinicians fail to manage procedural pain in infants more effectively. The objective of this study was to determine whether the magnitude of infants' responses to nursing/medical procedures: 1) differs as a function of the invasiveness or intensity of the procedure; 2) differs as a function of intrauterine (gestational age at birth) and/or extrauterine (conceptional age) development; and 3) parallels the subjective pain ratings of clinicians for those procedures. METHODS: A broad developmental and clinical range of newborn infants was studied shortly before (baseline and preparatory periods), throughout, and shortly after (recovery period) required nursing/medical procedures during hospitalization. Heart rate, oxygen saturation, mean arterial pressure, and behavioral state (percentage of time spent in sleep or in agitation) were measured, and the magnitude of change in each in response to procedures was calculated. Procedures were categorized as mildly, moderately, and highly invasive to examine differences in response magnitude as a function of procedural invasiveness. Responses were compared as a function of prematurity and postnatal age. Clinicians' procedural pain ratings were compared with the magnitude of infants' responses. RESULTS: Of the original 152 infants, 135 were studied at least two times (range 2-27). Significant changes occurred in physiologic and behavioral measures in response to procedures indicative of pain responses. The magnitude of response generally increased with increased procedural invasiveness although there was considerable overlap of magnitude with invasiveness. Both premature and full-term infants differentiated procedural invasiveness. Very premature infants (<28 weeks' gestational age) exhibited increased increments in response magnitude with increasing postnatal age. Clinician's ratings of procedural painfulness were correlated with and predicted the magnitude of heart rate response to individual procedures. CONCLUSIONS: Similar to what has been shown in adults, newborn and developing infants show increased magnitude physiologic and behavioral responses to increasingly invasive procedures, demonstrating that even very prematurely born infants respond to pain and differentiate stimulus intensity. However, the considerable overlap of magnitude with invasiveness suggests that there is not a physiologic or behavioral threshold that clearly marks the presence of pain. Inconsistencies in physiologic and behavioral responses make reliance on a pain index difficult. The best approach may be one of universal precaution to provide pain management systematically to reduce the acute and long-term impact of early procedural pain. development, stimulus intensity, pain response.