This study tested the factor structure of coping and stress responses in Navajo adolescents and examined the reliability and validity of the Responses to Stress Questionnaire (RSQ; Connor-Smith, Compas, Wadsworth, Thomsen, & Saltzman, 2000) with this population. Confirmatory factor analyses revealed that a correlated five-factor model of stress responses using the five factors of the RSQ fit the data well for this group of adolescents. The factor structure of the RSQ did not differ by gender. Internal consistency of the RSQ scales and factors was acceptable, and convergent and discriminant validity were moderate to high. Primary and secondary control engagement coping responses were associated with fewer depressive symptoms in the sample, whereas disengagement coping and involuntary engagement responses were associated with more depressive symptoms. The promising implications for stress and coping research with American Indian adolescents are emphasized. (Contains 2 figures and 3 tables.)