PURPOSE:To investigate the effects of life events, social support, and coping on anxiety and depression among human immunodeficiency virus (HIV)-infected adolescents. It was hypothesized that higher levels of stressful events would be associated with higher levels of anxiety and depression, but that this association would be moderated by satisfaction with social support and by adaptive coping. METHODS:HIV-infected adolescents from 16 locations in 13 U.S. cities (N = 230, median age 16.09 years, standard deviation 1.2, range 13-19; 77% females) were recruited into the Reaching for Excellence in Adolescent Care and Health (REACH) project. REACH is the first large-scale disease progression study of HIV(+) adolescents infected through sexual behavior or injection drug use. The adolescent assessment was conducted by audio-computer assisted self-interview. Least squares regressions were used to test hypotheses. RESULTS:Life events with high impact were associated with higher levels of depression and anxiety. Frequently reported events included: being prescribed medications (74%), family financial problems (61%), and parental alcohol abuse (20%). Contrary to expectations, the buffering hypotheses of social support and adaptive coping were not supported. Satisfaction with social support and adaptive coping methods were both associated directly with lower levels of depression, but no association was detected between these two measures and anxiety. CONCLUSIONS:Although life event distress was directly associated with psychological distress, neither social support nor adaptive coping seemed to moderate this association. However, both satisfaction with support and adaptive coping were associated directly with depression in HIV-infected adolescents.