As part of universal screening efforts in schools, validated measures that identify internalizing distress are needed. One promising available measure, the Depression, Anxiety, and Stress Scales-21 (DASS-21), has yet to be thoroughly investigated with adolescents in the United States. This study investigated the underlying factor structure of the DASS-21 in a sample of U.S. adolescents (N = 2,454) by using confirmatory factor analytic techniques to test several alternate models. A bifactor model specifying general "Negative Affectivity" and three specific factors of "Depression," "Anxiety," and "Stress" yielded the best fit. Results from this study suggest that (a) the DASS-21 scales reflect a common factor, indicating that a total score of the DASS-21 can be derived as a measure of general negative affectivity, and (b) the DASS-21 may not adequately differentiate between the experiences of negative affectivity, anxiety, and stress in U.S. adolescents.