The role of psychological interpretations in the relationship between low socioeconomic status (SES) and physiological responses was tested. One hundred high school students (ages 15-19) watched videos of ambiguous and negative life situations, and were interviewed about their interpretations. Lower SES was associated with greater threat interpretations during ambiguous (but not negative) situations and with greater diastolic blood pressure and heart rate reactivity. Threat interpretations partially mediated relationships between SES and reactivity. General life events (e.g., lack of positive life events), rather than specific life events (e.g., exposure to violence), partially explained the relationship between low SES and threat interpretations. Results suggest that the larger social environment helps explain how adolescents approach new social situations, which in turn has implications for adolescent physical health.