This study considers the interrelationships among coping, conflictual social interactions, and social support, as well as their combined associations with positive and negative mood. Research has shown that each of these variables affects adjustment to stressful circumstances. Few studies, however, examine this full set of variables simultaneously. One hundred forty HIV-infected persons completed a questionnaire containing measures of coping, social support, conflictual social interactions, and positive and negative mood. Factor analyses showed that perceived social support and conflictual social interactions formed separate factors and were not strongly related. Compared to perceived social support, social conflict was more strongly related to coping behaviors, especially to social isolation, anger, and wishful thinking. Conflictual social interactions were more strongly related to negative mood than was perceived social support. Coping by withdrawing socially was significantly related to less positive and greater negative mood. The findings point to the importance of simultaneously considering coping, supportive relationships, and conflictual relationships in studies of adjustment to chronic illness. In particular, a dynamic may occur in which conflictual social interactions and social isolation aggravate each other and result in escalating psychological distress.