The current study delineated patterns and predictors of adherence to antiretroviral therapy in 329 persons living with HIV disease in rural areas of 12 US states. Participants provided self-report data on patterns of HIV medication adherence, reasons for missing medication doses, psychological symptomatology, life-stressor burden, social support, ways of coping, coping self-efficacy, the quality of their relationship with their main physician, and barriers to health care and social services. Based on adherence data collected via retrospective, self-report assessment instruments, only 50% of participants adhered consistently to antiretroviral therapy regimens in the past week. Consistent adherence was more common in White participants, persons who had progressed to AIDS, and 'native infections' (i.e. persons who were born, raised, and infected in their current place of residence). Logistic regression analyses indicated that consistent adherence was reported by persons who drank less alcohol, had a good relationship with their main physician, and engaged in more active coping in response to HIV-related life stressors. As the number of rural persons living with HIV disease continues to increase, research that identifies correlates of non-adherence and conceptualizes approaches to optimize adherence in this group is urgently needed.