Personal, program-based, and environmental barriers to physical activity were explored among a U.S. population-derived sample of 2,912 women 40 years of age and older. Factors significantly associated with inactivity included American Indian ethnicity, older age, less education, lack of energy, lack of hills in one's neighborhood, absence of enjoyable scenery, and infrequent observation of others exercising in one's neighborhood. For all ethnic subgroups, caregiving duties and lacking energy to exercise ranked among the top 4 most frequently reported barriers. Approximately 62% of respondents rated exercise on one's own with instruction as more appealing than undertaking exercise in an instructor-led group, regardless of ethnicity or current physical activity levels. The results underscore the importance of a multifaceted approach to understanding physical activity determinants in this understudied, high-risk population segment.