The health inequalities experienced by Aboriginal and Torres Strait Islander Australians are well documented but there are few empirical data outlining the burden, consequences, experience and expression of depressive illness. This paper seeks to address the lack of accessible, culturally specific measures of psychosocial stress, depression or quality of life developed for, and validated within, this population.Building on an extensive qualitative phase of research, a psychosocial questionnaire comprising novel and adapted scales was developed and piloted with 189 Aboriginal men across urban and remote settings in central Australia. With a view to refining this tool for future use, its underlying structure was assessed using exploratory factor analysis, and the predictive ability of the emergent psychosocial constructs assessed with respect to depressive symptomatology.The latent structure of the psychosocial questionnaire was conceptually aligned with the components of the a priori model on which the questionnaire was based. Regression modelling indicated that depressive symptoms were driven by a sense of injury and chronic stress and had a non-linear association with socioeconomic position.This represents the first community-based survey of psychosocial stress and depression in Aboriginal men. It provides both knowledge of, and an appropriate process for, the further development of psychometric tools, including quality of life, in this population. Further research with larger and more diverse samples of Aboriginal people is required to refine the measurement of key constructs such as chronic stress, socioeconomic position, social support and connectedness. The further refinement, validation against criterion-based methods and incorporation within primary care services is essential.