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Reduced pain sensitivity is widely reported to be a common feature of children with autism, yet this conclusion frequently has been based on anecdotal observations and questionable measures of pain. The aims of the study were to (1) characterize the behavioral response of children with autism experiencing a venepuncture using objective observational measures of pain and distress, (2) examine parents’ assessments of pain behavior in children with and without autism, including comparison of the relationship of parental reports with behavioral measures, and (3) compare the behavioral reactions and parental assessments of children with autism with children without autism undergoing venepuncture.Pain reactions to the invasive procedure of venepuncture were videotaped, systematically described and compared in 21 children with autism (3–7 years old) and 22 nonimpaired children, the latter providing a chronological age and gender equivalent comparison group. Parents provided observer reports of pain, and facial activity was used as an objective behavioral measure of pain.The children with autism displayed a significant facial pain reaction in response to the venepuncture procedure. There was a lack of concordance between parental reports of pain and observed pain responses for the children with autism. Behavioral responses of the children with autism were generally similar to the comparison group, except the substantial facial pain reactivity instigated by the venepuncture in the children with autism exceeded that displayed by the nonimpaired comparison children. Parent reports of pain severity did not differ between the autism and comparison groups. The degree of concordance between parental report and observed pain responses was consistently better for the comparison group.The findings demonstrate that children with autism display a significant behavioral reaction in response to a painful stimulus, and these findings are in sharp contrast to the prevailing beliefs of pain insensitivity described in the literature to date. The findings also raise questions about the appropriateness of parental global report as an assessment tool for pain in children with autism.