Trends in the incidence of HIV/AIDS infection among women in Sub-Saharan Africa suggest this population is increasingly at risk. Many of the same factors that have predisposed rural African women to ill health in the past now increase their vulnerability to AIDS, including poverty and malnutrition, uncontrolled fertility, and complications of childbirth. As men travel out from rural communities to urban centers in search of employment, their sexual contacts multiply; many will acquire the HIV virus and carry it back to infect wives at home. Women, too, are leaving rural areas for the promise of a better life in cities and commercial centers along the way. Their struggle for economic survival and personal autonomy has led many to form relationships with new sexual partners, with a consequent increase in HIV seroprevalence among women once considered at low risk of infection. This paper argues that AIDS prevention campaigns have not yet taken into account the cultural, social, and economic constraints on most African women's ability to comply with advice to limit partners and use condoms. The author proposes a research agenda to explore the meaning of AIDS and AIDS prevention in the sociocultural context of women's lives. A better understanding of how women, themselves, perceive and respond to current attempts to prevent the transmission of AIDS is an increasingly critical factor in the intervention process. Most important, it is a necessary first step toward their effective participation with men in the development of culturally relevant strategies for protecting themselves and their families.