The present study tested whether individual differences in autonomic nervous system functioning interact with environmental risk factors to predict adolescents' psychosocial functioning. The authors assessed skin conductance and respiratory sinus arrhythmia at rest and during laboratory stressors in 110 14-year-olds. Subsequently, adolescents and their mothers provided both questionnaire and daily diary data (over 10 days) on emotional and interpersonal functioning. The authors found stronger associations between environmental risk factors (having a single-mother household or a mother with high internalizing problems) and psychosocial outcomes (externalizing problems, daily negative affect, and daily interaction quality) among youths with specific patterns of tonic and stress-induced sympathetic and parasympathetic nervous system activity, but the pattern of moderating effects differed between boys and girls. The findings support the notion that individual differences in autonomic functioning index variation in youth's susceptibility to environmental risk factors.