Investigated both positive and negative social interactions and their effect on mental health for 106 individuals caring for a seriously mentally ill family member. Results from mixed-model (hierarchial and stepwise) multiple regression analyses in which caregiver age, socioeconomic status, caregiving demand, and severity of patient symptoms was controlled showed that negative social interaction accounted for a significant portion of variance in the caregivers' feelings of distress and depression. Moderated multiple regression analyses showed that under conditions of high negative interaction, the relationship between demand and distress was intensified. Implications of these findings for the conceptualization and measurement of negative social interaction as well as its clinical implications were discussed.