This study examined the mechanism by which stressors, dissatisfaction with family, perceived control, social support, and coping were related to psychological distress in a sample of HIV-positive African American mothers. Additional analyses explored whether women who had a history of a drug abuse or dependence diagnosis differed either on levels of the study variables or the model pathways. The results indicated that HIV-positive African American mothers who had higher levels of stressors perceived their stressors as a whole to be less controllable. Coping resources, available social support and perceived control, were positively associated with active coping and negatively associated with psychological distress. Avoidant coping was the most important predictor of psychological distress. Furthermore, the effect of avoidant coping on psychological distress was stronger for mothers with a history of drug diagnosis. The implications of these findings for targeting interventions are discussed.