This study implements qualitative and quantitative methodologies in the development of a culturally appropriate instrument of stress for Mexican immigrant farmworkers. Focus groups were used to uncover culturally based perspectives on life stressors, definitions of stress, and stress mediators. Qualitative data were analyzed using QSR NVivo and then used to develop a 23-item stress scale. The scale was tested for reliability and validity in an independent sample and demonstrates excellent reliability (alpha = 0.9123). Test-retest coefficients of the stress scale are also strong (r = 0.8344, p = 0.0000). Qualitative analyses indicated three major sources of stress: work, family, and community. Emotional aspects of stress also emerged, demonstrating a cultural perspective of stress closely related to feelings of despair and not being able to find a way out of despairing situations. This paper reveals themes gathered from the qualitative data and identifies reliability and validity constructs associated with the scale. The stress scale developed as part of this investigation is a reliable and culturally appropriate instrument for assessing stress among Mexican immigrant farmworkers.