Factors associated with psychological distress were examined in 220 low-income, mostly minority mothers with late-stage HIV/AIDS. Mothers lived with at least one HIV-negative child of age 2-12 years and participated in a study of the effectiveness of a custody planning intervention provided by The Family Center. The mothers exhibited extraordinarily high levels of psychological disturbance on the Psychiatric Symptom Index (PSI). Multiple regression showed that higher PSI Total scores were significantly related to the mother's reports of having non-HIV-related medical conditions, spending time in bed in the past 2 weeks, having more activity restrictions, and having a lot of difficulty caring for her child due to ill health. Higher scores also were associated with lower education, experiencing more negative life events, and greater receipt and lower adequacy of social support. Thus, higher distress was associated with inability to perform usual activities and mobilization of support. However, other HIV-related health factors, traditional background characteristics, and psychosocial measures (e.g., HIV stigma, parenting stress, family environment) failed to indicate who was most vulnerable. Researchers need to identify the mechanisms of risk and develop appropriate mental health interventions.