Depressive symptoms are a common response to HIV disease, and women appear to be at particularly high risk. The authors report results from a cross-sectional analysis of data collected from 280 rural women with HIV/AIDS in the Southeastern United States aimed at identifying risk factors of depressive symptoms. Stress theory provided a framework for identification of potential risk factors. Descriptive statistics, measures of association, and regression analyses were used to systematically identify patterns of risk. The final regression model included 22 factors that accounted for 69% of the variance in depressive symptoms. The majority of variance in depressive symptoms was accounted for by only six variables: the frequency of HIV symptoms, recent experiences of sadness/hopelessness, the availability of social support, and the use of three coping strategies: living positively with HIV, isolation/withdrawal, and denial/avoidance. The results suggest a number of intervention strategies for use with rural women with HIV/AIDS.