Physiological responses may inform us about and help us to interpret behavioral responses. For example, hyperarousal may be a source of behavior problems in children with fragile X syndrome (FXS). To evaluate this approach, we examined heart period data in specific contexts in boys with FXS and in normally developing chronological-age-matched boys. Spectral analysis was used to evaluate the parasympathetic and sympathetic nervous systems' contributions to heart period. Boys with FXS had shorter interbeat intervals, lower parasympathetic activity, and similar sympathetic activity. Also, the groups were differentially responsive to experimental challenge. These results have important implications for our understanding of the basic nervous system dysfunction in FXS and for the strategies likely to be effective in terms of pharmacological intervention with these children. These methods can be applied to a variety of contexts and populations, including children who are sensory defensive, socially avoidant, inattentive, or hyperactive.