This study tested a conceptual model that integrates structural and psychological determinants of HIV prevention for African American women. The sample consisted of African American mothers (N = 129) of children in Head Start programs. Higher levels of perceived stress were associated with higher levels of HIV risk; higher levels of perceived racism were related to higher HIV prevention behavior. A combined psychological functioning score, representing levels of depression and anger, significantly moderated the relationships of perceived stress and racism to prevention behavior. This study confirms the importance of interactions between sociostructural factors and psychological factors as predictors of health behavioral outcomes and reinforces the need to examine the impact of structural factors on psychological functioning, perceived HIV risk, and HIV prevention behavior in African American women.