This study systematically assessed sensory processing in 34 children, aged 3-14 years, with Smith-Magenis syndrome (SMS) using the Sensory Profile Caregiver Questionnaire. Scores for the SMS cohort were significantly different from scores of the national sample of children with and without disabilities in all Sensory Profile categories and quadrants (p less than 0.001). No main effects of age or gender were found, but an interaction effect of age by gender was found in Modulation of Sensory Input Affecting Emotional Responses, in which older females presented with the lowest scores. A significant decline over time was found in the Seeking pattern, reflecting increased vulnerability (p less than 0.05). Nonsignificant trends suggest more vulnerabilities for older versus younger children, especially older females. The neurobehavioral phenotype in children with SMS is expanded by this description of sensory processing. How children with SMS experience and respond to everyday sensations informs multidisciplinary team decisions. (Contains 6 tables and 1 figure.)