The current study investigated differences in the development of temperament for normally developing infants and infants with Down Syndrome (DS). DS has been described as the most prevalent cause for mental retardation, and its effects on the central nervous system may also influence the development of temperament. Parents of 3 to 12 month-old normally developing infants and infants with DS completed the Infant Behavior Questionnaire-Revised (IBQ-R). Results indicated that parents of infants with DS described their children as exhibiting higher levels of temperament dimensions associated with Orienting/Regulating Capacity, and lower levels of attributes collectively referred to as Negative Affectivity, relative to comparison children. Specifically, infants with DS were reported to exhibit lower levels of Distress to Limitations, higher levels of Low Intensity Pleasure, Duration of Orienting, Falling Reactivity, and Cuddliness/Affiliation. No significant differences were found between IBQ-R factor intercorrelations for children with DS and normatively developing infants.