This study uses an integration of ethnographic and case-study qualitative analysis to help explain early adolescent and caregiver perspectives of an increased prevalence of depression in Mexican American girls. This phenomenon has been replicated in numerous other studies and it is important to obtain more information to inform understanding, enhance treatment, and initiate intervention and prevention strategies. The combination of these methods of qualitative inquiry allowed for the triangulation of multiple pieces of data including participant observation, interviewing, and archival research. Retrospective child and caregiver verbal accounts were compared with one another as well as with prior assessment of functioning and participant observation. Fourteen Mexican American or bi-ethnic early adolescents and one of their caregivers were interviewed using an unstructured interview process. Transcribed interviews were analyzed qualitatively. Findings suggest that both girls and caregivers focus on the contribution of negative life events, interpersonal relationship stress, personal characteristics, gender discrimination, and biology on the increased prevalence of depression. It is noteworthy that each of these factors is strongly correlated with the family socio-cultural environment. This study concludes with a proposal to integrate the work of Zayas, Lester, Cabassa, and Fortuna (2005) regarding Latina suicide attempts and the work of Hyde, Mezulis, and Abramson (2008) regarding the increase in girls’ rates of depression during early adolescence to explain the increased prevalence of depression in Mexican American girls yielding additional affective, biological, and cognitive vulnerabilities as well as particular negative life events. / text